{"gene":"SMARCA1","run_date":"2026-04-28T20:42:08","timeline":{"discoveries":[{"year":2006,"finding":"The PHD finger of BPTF (the large subunit of the NURF complex) directly binds trimethylated histone H3 lysine 4 (H3K4me3), coupling this epigenetic mark to recruitment of the associated ATPase SNF2L (SMARCA1) to target promoters such as HOXC8. Depletion of H3K4me3 causes partial release of BPTF from chromatin and defective recruitment of SNF2L, and loss of BPTF in Xenopus embryos compromises spatial control of Hox gene expression.","method":"Peptide pulldown, ChIP, Xenopus loss-of-function, co-immunoprecipitation","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, ChIP, in vivo loss-of-function in Xenopus, multiple orthogonal methods in one study","pmids":["16728976"],"is_preprint":false},{"year":2003,"finding":"Human SNF2L (SMARCA1) was purified as the ATPase catalytic subunit of a human NURF complex (hNURF) orthologous to Drosophila NURF. hNURF is enriched in brain tissue and directly regulates expression of the homeodomain protein Engrailed, potentiating neurite outgrowth in cell culture.","method":"Biochemical purification, immunoprecipitation, reporter gene assays, neurite outgrowth assay","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — purification to homogeneity, functional validation in cell culture, brain-enriched expression confirmed","pmids":["14609955"],"is_preprint":false},{"year":2005,"finding":"SNF2L (SMARCA1) forms a novel heterodimeric chromatin remodeling complex (CERF) with CECR2, a bromodomain- and DDT-domain-containing protein. CERF remodels chromatin in vitro and has nucleosome-stimulated ATPase activity. Loss of Cecr2 in mice causes exencephaly (neural tube defect), implicating SNF2L-containing CERF in neurulation.","method":"Biochemical co-purification, in vitro chromatin remodeling assay, ATPase assay, mouse genetrap knockout","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 1–2 — in vitro reconstitution of complex activity, murine loss-of-function with clear developmental phenotype","pmids":["15640247"],"is_preprint":false},{"year":2002,"finding":"Drosophila ISWI (ortholog of SMARCA1) activity is negatively regulated by acetylation of histone H4 at lysine 16 (H4K16ac). H4K16 acetylation reduces ISWI's ability to interact productively with its nucleosome substrate, as shown by peptide competition assays; blocking H4K16ac suppresses X-chromosome defects from ISWI loss, while forced H4K16ac in ISWI mutant females phenocopies ISWI mutant males.","method":"Drosophila genetics (epistasis), peptide competition ATPase assay, MOF overexpression","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 — genetic epistasis in Drosophila corroborated by biochemical peptide competition, replicated with multiple alleles","pmids":["11882543"],"is_preprint":false},{"year":2007,"finding":"The histone acetyltransferase GCN5 acetylates Drosophila ISWI (ortholog of SMARCA1) at a single conserved lysine (K753) in vivo and in vitro. The target sequence is similar to the N-terminus of histone H3 where GCN5 acetylates H3K14. Acetylated ISWI represents a minor species associated with the NURF complex.","method":"In vitro acetyltransferase assay, mass spectrometry, in vivo acetylation detection","journal":"BMC molecular biology","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro assay with identification of specific site, but single study with limited functional follow-up","pmids":["17760996"],"is_preprint":false},{"year":2009,"finding":"Xenopus/Drosophila ISWI (ortholog of SMARCA1) is a RanGTP-dependent microtubule-associated protein required for chromosome segregation. Recombinant ISWI induces MT nucleation, stabilization, and bundling in vitro. Depletion in Xenopus egg extracts leads to spindle MT disappearance and failed chromosome segregation in anaphase; depletion in Drosophila S2 cells causes spindle defects and growth arrest. ISWI localizes to spindles during mitosis, distinct from its interphase chromatin role.","method":"Xenopus egg extract depletion, in vitro MT assembly assay, RNAi in Drosophila S2 cells, live imaging","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 — in vitro reconstitution of MT activities, loss-of-function in two model systems with clear mitotic phenotype","pmids":["20008562"],"is_preprint":false},{"year":2012,"finding":"ISWI (ortholog of SMARCA1) is regulated by two conserved inhibitory domains: AutoN (inhibits ATP hydrolysis) and NegC (uncouples ATP hydrolysis from productive DNA translocation). The H4 basic patch on nucleosomes antagonizes AutoN, and extranucleosomal DNA antagonizes NegC, enabling remodeling only on appropriate chromatin substrates. Mutation or removal of AutoN and NegC confers SWI/SNF-like biochemical attributes on ISWI.","method":"ATPase assays, nucleosome sliding assays, domain deletion/mutagenesis in Drosophila ISWI","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 — reconstituted in vitro with mutagenesis, multiple functional assays, mechanistic model validated","pmids":["23143334"],"is_preprint":false},{"year":2016,"finding":"Crystal structures of ISWI from thermophilic yeast Myceliophthora thermophila reveal that the AutoN domain contains two inhibitory elements that bind the second RecA-like domain (core2), holding ISWI in an inactive conformation. The histone H4 peptide binds to core2 at a site coincident with one AutoN-binding site, explaining H4-tail-dependent activation. The NegC domain contacts core2 as an allosteric element responding to extranucleosomal DNA length.","method":"X-ray crystallography, structure-function mutagenesis, peptide binding assays","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 — atomic-resolution crystal structure with functional mutagenesis validation","pmids":["27919072"],"is_preprint":false},{"year":2019,"finding":"Cryo-EM structures of yeast ISW1 (ISWI ortholog of SMARCA1) in ADP-bound and ADP-BeFx-bound states show that nucleosome binding activates ISW1 via substantial rearrangement of catalytic domains. The AutoN domain packs against the first RecA-like core and NegC becomes disordered upon activation. Local DNA distortion and translocation occurs without notable histone deformation, suggesting a general mechanism of chromatin remodeling involving DNA distortion independent of histone displacement.","method":"Cryo-EM at 3.3 Å resolution, crosslinking assays to prevent histone distortion","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 — near-atomic cryo-EM structure with mechanistic functional validation","pmids":["30872815"],"is_preprint":false},{"year":2017,"finding":"Mapping of the H4-tail binding pocket of ISWI (ortholog of SMARCA1) reveals that AutoN does not act as a simple pseudosubstrate competing with H4. Instead, AutoN cooperates with a second motif (AcidicN) to confer H4-tail sensitivity and discriminate nucleosomes from free DNA. A third N-terminal region motif (ppHSA) stabilizes the NTR by clamping it to Lobe 2 of the ATPase domain and is required in vivo.","method":"Mutagenesis, in vitro ATPase and sliding assays, cross-linking, in vivo complementation in Drosophila","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1–2 — mutagenesis combined with in vitro reconstitution and in vivo validation","pmids":["28109157"],"is_preprint":false},{"year":2017,"finding":"Each endogenously expressed ISWI ATPase (including SNF2L/SMARCA1) co-purifies with every regulatory subunit, substantially expanding the diversity of ISWI complexes beyond previously known pairings. SNF2L forms stable, direct complexes with all tested regulatory subunits. BAZ2B was identified as a novel seventh regulatory subunit. Reconstituted human ISWI complexes containing SNF2L showed nucleosome remodeling activity.","method":"Endogenous co-purification, reconstitution of catalytically active complexes, nucleosome remodeling assays","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 — reconstitution with functional validation, but SNF2L-specific functional data not distinguished from SNF2H in all assays","pmids":["28801535"],"is_preprint":false},{"year":2016,"finding":"Whole-genome sequencing of multiplex families with psychotic disorders identified a novel private missense variant in SMARCA1 (on the X chromosome) segregating with illness in four affected siblings and their unaffected mother. The variant alters the SMARCA1 protein sequence and is considered a candidate causal mutation for schizophrenia spectrum disorders in this family.","method":"Whole-genome sequencing, familial segregation analysis","journal":"Molecular psychiatry","confidence":"Low","confidence_rationale":"Tier 4 — genetic association without experimental functional validation of the variant's effect on SMARCA1 protein","pmids":["27001614"],"is_preprint":false},{"year":2018,"finding":"LncRNA DLEU1 promotes colorectal cancer progression by recruiting SMARCA1 (SNF2L, a subunit of the NURF chromatin remodeling complex) to the promoter of KPNA3, activating its transcription. Biotin-coupled probe pulldown, RNA immunoprecipitation, and FISH confirmed direct interaction between DLEU1 and SMARCA1. DLEU1 knockdown reduced SMARCA1 deposition at the KPNA3 promoter.","method":"RNA immunoprecipitation, biotin-probe pulldown, ChIP, FISH, shRNA knockdown with phenotypic rescue","journal":"Molecular cancer","confidence":"Medium","confidence_rationale":"Tier 2–3 — multiple biochemical methods confirm DLEU1-SMARCA1 interaction and promoter recruitment, but mechanistic dissection is limited","pmids":["30098595"],"is_preprint":false},{"year":2017,"finding":"Review and genetic analysis of Smarca1 knockout mice establishes that SMARCA1 (SNF2L) is required for proper brain development. Loss of SMARCA1 function has been implicated in neurodevelopmental disorders, and ISWI complex-mediated nucleosome positioning within gene regulatory elements is important for the transition from committed neural progenitor states to differentiated cell states.","method":"Mouse knockout analysis, genetic studies","journal":"Molecular and cellular neurosciences","confidence":"Low","confidence_rationale":"Tier 3 — review summarizing mouse KO phenotypes without primary mechanistic data in this paper","pmids":["29249292"],"is_preprint":false}],"current_model":"SMARCA1 (SNF2L) is the catalytic ATPase subunit of the mammalian NURF and CERF chromatin remodeling complexes; it is recruited to H3K4me3-marked chromatin via the BPTF PHD finger, remodels nucleosomes through an ATP-dependent DNA translocation mechanism regulated by inhibitory AutoN and NegC domains that are antagonized by the histone H4 tail and extranucleosomal DNA respectively, and functions beyond chromatin remodeling as a RanGTP-dependent microtubule-associated protein required for anaphase chromosome segregation."},"narrative":{"teleology":[{"year":2002,"claim":"Establishing how the nucleosome substrate regulates ISWI activity: H4K16 acetylation was shown to antagonize ISWI function, revealing that the unmodified H4 tail is a critical activating signal for the ATPase.","evidence":"Drosophila genetic epistasis combined with peptide competition ATPase assays","pmids":["11882543"],"confidence":"High","gaps":["Whether the H4K16ac effect is direct on the mammalian SNF2L enzyme was not tested","The structural basis for H4-tail recognition was unknown"]},{"year":2003,"claim":"Identifying the biological context of mammalian SMARCA1: purification of human NURF (hNURF) established SNF2L as its ATPase subunit, showed enrichment in brain, and linked the complex to Engrailed-dependent neurite outgrowth.","evidence":"Biochemical purification, reporter assays, and neurite outgrowth in cultured cells","pmids":["14609955"],"confidence":"High","gaps":["In vivo requirement for hNURF in mammalian brain development was not demonstrated","How SNF2L is targeted to Engrailed regulatory elements was unclear"]},{"year":2005,"claim":"Expanding the repertoire of SMARCA1 complexes: discovery of CERF (CECR2–SNF2L) demonstrated that SMARCA1 functions in a second remodeling complex, and Cecr2 knockout mice linked this complex to neurulation.","evidence":"Co-purification, in vitro remodeling assays, and mouse genetrap knockout causing exencephaly","pmids":["15640247"],"confidence":"High","gaps":["Whether CERF has distinct genomic targets from NURF was unknown","The contribution of SNF2L catalytic activity versus CECR2 scaffolding was not dissected"]},{"year":2006,"claim":"Determining how SMARCA1 is targeted to active chromatin: the PHD finger of BPTF was shown to read H3K4me3, coupling this epigenetic mark to NURF/SNF2L recruitment at Hox gene promoters.","evidence":"Peptide pulldown, ChIP, and Xenopus loss-of-function","pmids":["16728976"],"confidence":"High","gaps":["Whether H3K4me3-directed recruitment is the sole targeting mechanism for SNF2L was not resolved","Mammalian in vivo validation was lacking"]},{"year":2009,"claim":"Revealing a non-chromatin function: ISWI/SMARCA1 ortholog was identified as a RanGTP-dependent microtubule-associated protein that nucleates and bundles microtubules, with depletion causing spindle collapse and failed anaphase chromosome segregation.","evidence":"In vitro MT assembly reconstitution, Xenopus egg extract depletion, Drosophila S2 cell RNAi, and live imaging","pmids":["20008562"],"confidence":"High","gaps":["Whether mammalian SMARCA1 retains the mitotic MT function was not shown","The relationship between chromatin remodeling and MT-stabilizing activities is unresolved"]},{"year":2012,"claim":"Defining the autoinhibitory mechanism: two conserved domains (AutoN and NegC) were shown to suppress ATPase activity and productive DNA translocation, respectively, and are antagonized by the H4 basic patch and extranucleosomal DNA—explaining why ISWI remodels only appropriate nucleosomal substrates.","evidence":"Domain deletion/mutagenesis with in vitro ATPase and nucleosome sliding assays on Drosophila ISWI","pmids":["23143334"],"confidence":"High","gaps":["Structural basis for AutoN and NegC inhibition was not yet available","Whether human SNF2L autoinhibition follows identical rules was assumed but not directly tested"]},{"year":2016,"claim":"Providing the structural basis for autoinhibition and H4-tail activation: crystal structures revealed that AutoN binds RecA-like core2 to lock ISWI in an inactive state, and the H4 tail competes at an overlapping binding site to relieve inhibition.","evidence":"X-ray crystallography of M. thermophila ISWI with structure-function mutagenesis","pmids":["27919072"],"confidence":"High","gaps":["Full nucleosome-bound structure was not obtained","NegC relief mechanism upon extranucleosomal DNA sensing lacked atomic detail"]},{"year":2017,"claim":"Refining the N-terminal regulatory region: AutoN was shown not to be a simple pseudosubstrate; instead it cooperates with AcidicN and ppHSA motifs to confer H4-tail sensitivity and discriminate nucleosomes from free DNA, with ppHSA required in vivo.","evidence":"Mutagenesis, in vitro ATPase/sliding assays, cross-linking, Drosophila in vivo complementation","pmids":["28109157"],"confidence":"High","gaps":["How AcidicN and ppHSA are affected by post-translational modifications is unknown","Whether regulatory subunits modulate AutoN/NegC gating was not addressed"]},{"year":2017,"claim":"Expanding ISWI complex combinatorics: endogenous co-purification showed SNF2L can pair with every known ISWI regulatory subunit (including a novel partner BAZ2B), vastly increasing the diversity of SMARCA1-containing complexes.","evidence":"Endogenous co-purification and reconstitution of active complexes with nucleosome remodeling assays","pmids":["28801535"],"confidence":"Medium","gaps":["Functional specificity of each SNF2L-containing complex was not distinguished","In vivo relevance of BAZ2B–SNF2L pairing was not established"]},{"year":2019,"claim":"Visualizing the remodeling mechanism at near-atomic resolution: cryo-EM structures of nucleosome-bound ISW1 revealed that substrate binding triggers major rearrangement of catalytic domains with AutoN repacking and NegC disordering, and that DNA is translocated with local distortion but without notable histone deformation.","evidence":"Cryo-EM at 3.3 Å resolution with crosslinking-based functional validation","pmids":["30872815"],"confidence":"High","gaps":["Structures of mammalian SNF2L on nucleosomes are still lacking","Transition-state intermediates during the full translocation cycle were not captured"]},{"year":null,"claim":"Key unresolved questions include: the genomic target specificity and non-redundancy of each SMARCA1-containing complex in mammalian tissues; whether the mitotic microtubule function of SMARCA1 is conserved and physiologically relevant in mammals; and the mechanistic contribution of SMARCA1 variants to neurodevelopmental and psychiatric disease.","evidence":"","pmids":[],"confidence":"Low","gaps":["No mammalian conditional knockout systematically comparing complex-specific phenotypes","Mitotic MT role not tested in mammalian cells","Disease-linked SMARCA1 variants lack functional validation"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[1,2,6,7,8,9]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[6,8]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[3,6,7,9]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[5]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1,12]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,5]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[5]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,1,2,6,8,10]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1,12]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,2,13]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[5]}],"complexes":["NURF","CERF"],"partners":["BPTF","CECR2","BAZ2B","DLEU1"],"other_free_text":[]},"mechanistic_narrative":"SMARCA1 (SNF2L) is the catalytic ATPase subunit of multiple ISWI-family chromatin remodeling complexes—including NURF and CERF—that reposition nucleosomes to regulate gene expression during neural development and other processes [PMID:14609955, PMID:15640247, PMID:28801535]. Its remodeling activity is gated by two conserved autoinhibitory domains, AutoN and NegC, which restrict ATP hydrolysis and productive DNA translocation, respectively; these are relieved by the histone H4 basic patch and extranucleosomal DNA, ensuring substrate-specific activation [PMID:23143334, PMID:27919072, PMID:30872815]. SMARCA1 is recruited to H3K4me3-marked chromatin via the PHD finger of its NURF partner BPTF and can also be guided to specific promoters by lncRNAs such as DLEU1 [PMID:16728976, PMID:30098595]. Beyond its chromatin role, the ISWI ortholog functions as a RanGTP-dependent microtubule-associated protein required for spindle integrity and anaphase chromosome segregation [PMID:20008562]."},"prefetch_data":{"uniprot":{"accession":"P28370","full_name":"SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 1","aliases":["Global transcription activator SNF2L1","Nucleosome-remodeling factor subunit SNF2L","SNF2L","SNF2 related chromatin remodeling ATPase 1"],"length_aa":1042,"mass_kda":121.1,"function":"ATPase that possesses intrinsic ATP-dependent chromatin-remodeling activity (PubMed:14609955, PubMed:15310751, PubMed:15640247, PubMed:28801535). ATPase activity is substrate-dependent, and is increased when nucleosomes are the substrate, but is also catalytically active when DNA alone is the substrate (PubMed:14609955, PubMed:15310751, PubMed:15640247). Catalytic subunit of ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:14609955, PubMed:15310751, PubMed:15640247, PubMed:28801535). Within the ISWI chromatin-remodeling complexes, slides edge- and center-positioned histone octamers away from their original location on the DNA template (PubMed:28801535). Catalytic activity and histone octamer sliding propensity is regulated and determined by components of the ISWI chromatin-remodeling complexes (PubMed:28801535). The BAZ1A-, BAZ1B-, BAZ2A- and BAZ2B-containing ISWI chromatin-remodeling complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The CECR2- and RSF1-containing ISWI chromatin-remodeling complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Within the NURF-1 and CERF-1 ISWI chromatin remodeling complexes, nucleosomes are the preferred substrate for its ATPase activity (PubMed:14609955, PubMed:15640247). Within the NURF-1 ISWI chromatin-remodeling complex, binds to the promoters of En1 and En2 to positively regulate their expression and promote brain development (PubMed:14609955). May promote neurite outgrowth (PubMed:14609955). May be involved in the development of luteal cells (PubMed:16740656). Facilitates nucleosome assembly during DNA replication, ensuring replication fork progression and genomic stability by preventing replication stress and nascent DNA gaps (PubMed:39413208) Catalytically inactive when either DNA or nucleosomes are the substrate and does not possess chromatin-remodeling activity (PubMed:15310751, PubMed:28801535). Acts as a negative regulator of chromatin remodelers by generating inactive complexes (PubMed:15310751)","subcellular_location":"Nucleus; Chromosome","url":"https://www.uniprot.org/uniprotkb/P28370/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SMARCA1","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000102038","cell_line_id":"CID001670","localizations":[{"compartment":"nucleoplasm","grade":3},{"compartment":"chromatin","grade":2},{"compartment":"cytoplasmic","grade":1}],"interactors":[{"gene":"CHRAC1","stoichiometry":10.0},{"gene":"CECR2","stoichiometry":10.0},{"gene":"NUCKS1","stoichiometry":4.0},{"gene":"BAP18;C17ORF49;RNASEK-C17ORF49","stoichiometry":4.0},{"gene":"HMGXB4","stoichiometry":4.0},{"gene":"POLE3","stoichiometry":4.0},{"gene":"BAZ1A","stoichiometry":4.0},{"gene":"BAZ1B","stoichiometry":4.0},{"gene":"RSF1","stoichiometry":4.0},{"gene":"BPTF","stoichiometry":4.0}],"url":"https://opencell.sf.czbiohub.org/target/CID001670","total_profiled":1310},"omim":[{"mim_id":"613325","title":"RHABDOID TUMOR PREDISPOSITION SYNDROME 2; RTPS2","url":"https://www.omim.org/entry/613325"},{"mim_id":"607576","title":"CECR2 HISTONE ACETYL-LYSINE READER; CECR2","url":"https://www.omim.org/entry/607576"},{"mim_id":"603946","title":"HELICASE, LYMPHOID-SPECIFIC; HELLS","url":"https://www.omim.org/entry/603946"},{"mim_id":"602810","title":"HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER A; HIST1H3A","url":"https://www.omim.org/entry/602810"},{"mim_id":"601819","title":"BROMODOMAIN PHD FINGER TRANSCRIPTION FACTOR; BPTF","url":"https://www.omim.org/entry/601819"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SMARCA1"},"hgnc":{"alias_symbol":["SNF2LB","NURF140","ISWI","SWI","hSNF2L"],"prev_symbol":["SNF2L1","SNF2L"]},"alphafold":{"accession":"P28370","domains":[{"cath_id":"3.40.50.10810","chopping":"184-398","consensus_level":"high","plddt":83.2167,"start":184,"end":398},{"cath_id":"3.40.50.300","chopping":"409-738","consensus_level":"high","plddt":77.9614,"start":409,"end":738},{"cath_id":"1.10.1040.30","chopping":"787-918","consensus_level":"medium","plddt":87.5536,"start":787,"end":918},{"cath_id":"1.10.10.60","chopping":"926-1038","consensus_level":"high","plddt":87.6412,"start":926,"end":1038}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P28370","model_url":"https://alphafold.ebi.ac.uk/files/AF-P28370-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P28370-F1-predicted_aligned_error_v6.png","plddt_mean":74.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SMARCA1","jax_strain_url":"https://www.jax.org/strain/search?query=SMARCA1"},"sequence":{"accession":"P28370","fasta_url":"https://rest.uniprot.org/uniprotkb/P28370.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P28370/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P28370"}},"corpus_meta":[{"pmid":"30343899","id":"PMC_30343899","title":"Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes.","date":"2018","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/30343899","citation_count":586,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9230310","id":"PMC_9230310","title":"ACF, an ISWI-containing and ATP-utilizing chromatin assembly and remodeling factor.","date":"1997","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/9230310","citation_count":527,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19234488","id":"PMC_19234488","title":"The SWI/SNF complex and cancer.","date":"2009","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/19234488","citation_count":470,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9252192","id":"PMC_9252192","title":"Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II.","date":"1997","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/9252192","citation_count":436,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"6436497","id":"PMC_6436497","title":"Five SWI genes are required for expression of the HO gene in yeast.","date":"1984","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/6436497","citation_count":373,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10399913","id":"PMC_10399913","title":"Nucleosome movement by CHRAC and ISWI without disruption or trans-displacement of the histone octamer.","date":"1999","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/10399913","citation_count":296,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30401838","id":"PMC_30401838","title":"The SWI/SNF complex is a mechanoregulated inhibitor of YAP and TAZ.","date":"2018","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/30401838","citation_count":256,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25387058","id":"PMC_25387058","title":"SWI/SNF chromatin remodeling and human malignancies.","date":"2014","source":"Annual review of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/25387058","citation_count":250,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12434153","id":"PMC_12434153","title":"An ACF1-ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin.","date":"2002","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/12434153","citation_count":249,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34937944","id":"PMC_34937944","title":"Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34937944","citation_count":246,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16518397","id":"PMC_16518397","title":"Chromatin remodeling by ISW2 and SWI/SNF requires DNA translocation inside the nucleosome.","date":"2006","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/16518397","citation_count":213,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30996347","id":"PMC_30996347","title":"Mammalian ISWI and SWI/SNF selectively mediate binding of distinct transcription factors.","date":"2019","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/30996347","citation_count":204,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12837955","id":"PMC_12837955","title":"PIE1, an ISWI family gene, is required for FLC activation and floral repression in Arabidopsis.","date":"2003","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/12837955","citation_count":200,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12620227","id":"PMC_12620227","title":"SWI/SNF unwraps, slides, and rewraps the nucleosome.","date":"2003","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/12620227","citation_count":195,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32958894","id":"PMC_32958894","title":"COMPASS and SWI/SNF complexes in development and disease.","date":"2020","source":"Nature reviews. Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/32958894","citation_count":192,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8587611","id":"PMC_8587611","title":"DNA-binding properties of the yeast SWI/SNF complex.","date":"1996","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/8587611","citation_count":184,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11882543","id":"PMC_11882543","title":"Modulation of ISWI function by site-specific histone acetylation.","date":"2002","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/11882543","citation_count":180,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28824374","id":"PMC_28824374","title":"Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders.","date":"2017","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/28824374","citation_count":174,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11420722","id":"PMC_11420722","title":"When the SWI/SNF complex remodels...the cell cycle.","date":"2001","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/11420722","citation_count":171,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11683384","id":"PMC_11683384","title":"Nucleosome mobilization and positioning by ISWI-containing chromatin-remodeling factors.","date":"2001","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/11683384","citation_count":162,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24932742","id":"PMC_24932742","title":"A rationale to target the SWI/SNF complex for cancer therapy.","date":"2014","source":"Trends in genetics : TIG","url":"https://pubmed.ncbi.nlm.nih.gov/24932742","citation_count":153,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31123059","id":"PMC_31123059","title":"Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer.","date":"2019","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/31123059","citation_count":144,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11790558","id":"PMC_11790558","title":"SWI/SNF chromatin remodeling and cancer.","date":"2002","source":"Current opinion in genetics & development","url":"https://pubmed.ncbi.nlm.nih.gov/11790558","citation_count":143,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22952240","id":"PMC_22952240","title":"SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22952240","citation_count":139,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25169151","id":"PMC_25169151","title":"SWI/SNF chromatin remodeling complexes and cancer.","date":"2014","source":"American journal of medical genetics. Part C, Seminars in medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25169151","citation_count":134,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32188938","id":"PMC_32188938","title":"Cryo-EM structure of SWI/SNF complex bound to a nucleosome.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32188938","citation_count":129,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23143334","id":"PMC_23143334","title":"Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes.","date":"2012","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/23143334","citation_count":128,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33941852","id":"PMC_33941852","title":"Exploiting vulnerabilities of SWI/SNF chromatin remodelling complexes for cancer therapy.","date":"2021","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/33941852","citation_count":123,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12612068","id":"PMC_12612068","title":"Evidence for DNA translocation by the ISWI chromatin-remodeling enzyme.","date":"2003","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12612068","citation_count":123,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24165726","id":"PMC_24165726","title":"Linking the SWI/SNF complex to prostate cancer.","date":"2013","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24165726","citation_count":114,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18644858","id":"PMC_18644858","title":"Architecture of the SWI/SNF-nucleosome complex.","date":"2008","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/18644858","citation_count":111,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26836503","id":"PMC_26836503","title":"PRC2 and SWI/SNF Chromatin Remodeling Complexes in Health and Disease.","date":"2016","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26836503","citation_count":110,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32188943","id":"PMC_32188943","title":"Structure of SWI/SNF chromatin remodeller RSC bound to a nucleosome.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32188943","citation_count":106,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17292979","id":"PMC_17292979","title":"SWI/SNF chromatin remodeling and linker histones in plants.","date":"2007","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/17292979","citation_count":102,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17101803","id":"PMC_17101803","title":"Functional differentiation of SWI/SNF remodelers in transcription and cell cycle control.","date":"2006","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17101803","citation_count":101,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15743818","id":"PMC_15743818","title":"BAF57 governs androgen receptor action and androgen-dependent proliferation through SWI/SNF.","date":"2005","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/15743818","citation_count":98,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25486562","id":"PMC_25486562","title":"ISWI chromatin remodeling complexes in the DNA damage response.","date":"2014","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/25486562","citation_count":97,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30897376","id":"PMC_30897376","title":"SWI/SNF: Complex complexes in genome stability and cancer.","date":"2019","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/30897376","citation_count":89,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26920655","id":"PMC_26920655","title":"The Role of SWI/SNF Chromatin Remodeling Complexes in Hormone Crosstalk.","date":"2016","source":"Trends in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/26920655","citation_count":88,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30872815","id":"PMC_30872815","title":"Structures of the ISWI-nucleosome complex reveal a conserved mechanism of chromatin remodeling.","date":"2019","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/30872815","citation_count":84,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17431399","id":"PMC_17431399","title":"A novel ISWI is involved in VSG expression site downregulation in African trypanosomes.","date":"2007","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/17431399","citation_count":84,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27001614","id":"PMC_27001614","title":"Whole-genome sequencing in multiplex families with psychoses reveals mutations in the SHANK2 and SMARCA1 genes segregating with illness.","date":"2016","source":"Molecular psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/27001614","citation_count":83,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28801535","id":"PMC_28801535","title":"Expansion of the ISWI chromatin remodeler family with new active complexes.","date":"2017","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/28801535","citation_count":81,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21810179","id":"PMC_21810179","title":"Chromatin remodelling in mammalian cells by ISWI-type complexes--where, when and why?","date":"2011","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/21810179","citation_count":77,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27919072","id":"PMC_27919072","title":"Structure and regulation of the chromatin remodeller ISWI.","date":"2016","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/27919072","citation_count":74,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10441072","id":"PMC_10441072","title":"The mammalian SWI/SNF complex and the control of cell growth.","date":"1999","source":"Seminars in cell & developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/10441072","citation_count":73,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28249160","id":"PMC_28249160","title":"Loss of Snf5 Induces Formation of an Aberrant SWI/SNF Complex.","date":"2017","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/28249160","citation_count":71,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23468649","id":"PMC_23468649","title":"ISWI and CHD chromatin remodelers bind promoters but act in gene bodies.","date":"2013","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23468649","citation_count":70,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34736517","id":"PMC_34736517","title":"The emerging role of ISWI chromatin remodeling complexes in cancer.","date":"2021","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/34736517","citation_count":68,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15284901","id":"PMC_15284901","title":"Functional diversity of ISWI complexes.","date":"2004","source":"Biochemistry and cell biology = Biochimie et biologie cellulaire","url":"https://pubmed.ncbi.nlm.nih.gov/15284901","citation_count":68,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9730600","id":"PMC_9730600","title":"Cloning and mapping of SMARCA5 encoding hSNF2H, a novel human homologue of Drosophila ISWI.","date":"1998","source":"Cytogenetics and cell genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9730600","citation_count":68,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31977292","id":"PMC_31977292","title":"SWI/SNF Complex Mutations in Gynecologic Cancers: Molecular Mechanisms and Models.","date":"2020","source":"Annual review of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/31977292","citation_count":66,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28068325","id":"PMC_28068325","title":"TRIM28 interacts with EZH2 and SWI/SNF to activate genes that promote mammosphere formation.","date":"2017","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/28068325","citation_count":66,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30962207","id":"PMC_30962207","title":"FET family fusion oncoproteins target the SWI/SNF chromatin remodeling complex.","date":"2019","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/30962207","citation_count":65,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37922899","id":"PMC_37922899","title":"Global identification of SWI/SNF targets reveals compensation by EP400.","date":"2023","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/37922899","citation_count":64,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25533843","id":"PMC_25533843","title":"Opposing ISWI- and CHD-class chromatin remodeling activities orchestrate heterochromatic DNA repair.","date":"2014","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/25533843","citation_count":64,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"36889009","id":"PMC_36889009","title":"The Role and Activity of SWI/SNF Chromatin Remodelers.","date":"2023","source":"Annual review of plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/36889009","citation_count":63,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24990377","id":"PMC_24990377","title":"Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription.","date":"2014","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/24990377","citation_count":62,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28249159","id":"PMC_28249159","title":"Composition and Function of Mutant Swi/Snf Complexes.","date":"2017","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/28249159","citation_count":61,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37225980","id":"PMC_37225980","title":"Mitotic bookmarking by SWI/SNF subunits.","date":"2023","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/37225980","citation_count":56,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33303640","id":"PMC_33303640","title":"Pioneer-like factor GAF cooperates with PBAP (SWI/SNF) and NURF (ISWI) to regulate transcription.","date":"2020","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/33303640","citation_count":55,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23752187","id":"PMC_23752187","title":"The SWI/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases.","date":"2013","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/23752187","citation_count":55,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30664740","id":"PMC_30664740","title":"Xist RNA antagonizes the SWI/SNF chromatin remodeler BRG1 on the inactive X chromosome.","date":"2019","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/30664740","citation_count":55,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29249292","id":"PMC_29249292","title":"The role of ISWI chromatin remodeling complexes in brain development and neurodevelopmental disorders.","date":"2017","source":"Molecular and cellular neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/29249292","citation_count":54,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38016477","id":"PMC_38016477","title":"Epigenetic pioneering by SWI/SNF family remodelers.","date":"2023","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/38016477","citation_count":52,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"36810086","id":"PMC_36810086","title":"SWI/SNF complexes in hematological malignancies: biological implications and therapeutic opportunities.","date":"2023","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/36810086","citation_count":51,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29397238","id":"PMC_29397238","title":"Hereditary SWI/SNF complex deficiency syndromes.","date":"2018","source":"Seminars in diagnostic pathology","url":"https://pubmed.ncbi.nlm.nih.gov/29397238","citation_count":50,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35537449","id":"PMC_35537449","title":"NSD1 mediates antagonism between SWI/SNF and polycomb complexes and is required for transcriptional activation upon EZH2 inhibition.","date":"2022","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/35537449","citation_count":47,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20015969","id":"PMC_20015969","title":"Functional interplay between chromatin remodeling complexes RSC, SWI/SNF and ISWI in regulation of yeast heat shock genes.","date":"2009","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/20015969","citation_count":47,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38538798","id":"PMC_38538798","title":"Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF.","date":"2024","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/38538798","citation_count":46,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30723142","id":"PMC_30723142","title":"Trabectedin Inhibits EWS-FLI1 and Evicts SWI/SNF from Chromatin in a Schedule-dependent Manner.","date":"2019","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/30723142","citation_count":45,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11304548","id":"PMC_11304548","title":"The interactions of yeast SWI/SNF and RSC with the nucleosome before and after chromatin remodeling.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11304548","citation_count":45,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20008562","id":"PMC_20008562","title":"ISWI is a RanGTP-dependent MAP required for chromosome segregation.","date":"2009","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/20008562","citation_count":44,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32358072","id":"PMC_32358072","title":"Dual Recognition of H3K4me3 and DNA by the ISWI Component ARID5 Regulates the Floral Transition in Arabidopsis.","date":"2020","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/32358072","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28276606","id":"PMC_28276606","title":"The ISWI ATPase Smarca5 (Snf2h) Is Required for Proliferation and Differentiation of Hematopoietic Stem and Progenitor Cells.","date":"2017","source":"Stem cells (Dayton, Ohio)","url":"https://pubmed.ncbi.nlm.nih.gov/28276606","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24145903","id":"PMC_24145903","title":"The SWI/SNF tumor suppressor complex: Regulation of promoter nucleosomes and beyond.","date":"2013","source":"Nucleus (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/24145903","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25774356","id":"PMC_25774356","title":"Beyond Mutations: Additional Mechanisms and Implications of SWI/SNF Complex Inactivation.","date":"2015","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/25774356","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30037854","id":"PMC_30037854","title":"SWI/SNF Complexes in Ovarian Cancer: Mechanistic Insights and Therapeutic Implications.","date":"2018","source":"Molecular cancer research : MCR","url":"https://pubmed.ncbi.nlm.nih.gov/30037854","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24913006","id":"PMC_24913006","title":"The silencing of the SWI/SNF subunit and anticancer gene BRM in Rhabdoid tumors.","date":"2014","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/24913006","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15201272","id":"PMC_15201272","title":"ATP-dependent remodeling by SWI/SNF and ISWI proteins stimulates V(D)J cleavage of 5 S arrays.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15201272","citation_count":38,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17760996","id":"PMC_17760996","title":"Site-specific acetylation of ISWI by GCN5.","date":"2007","source":"BMC molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17760996","citation_count":38,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15753658","id":"PMC_15753658","title":"Chromatin remodeling by WSTF-ISWI at the replication site: opening a window of opportunity for epigenetic inheritance?","date":"2005","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/15753658","citation_count":35,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20553711","id":"PMC_20553711","title":"SWI/SNF complexes, chromatin remodeling and skeletal myogenesis: it's time to exchange!","date":"2010","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/20553711","citation_count":33,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24561830","id":"PMC_24561830","title":"ISWI chromatin remodeling: one primary actor or a coordinated effort?","date":"2014","source":"Current opinion in structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/24561830","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38390898","id":"PMC_38390898","title":"Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications.","date":"2024","source":"Epigenomes","url":"https://pubmed.ncbi.nlm.nih.gov/38390898","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24498324","id":"PMC_24498324","title":"Epigenetic control of SPI1 gene by CTCF and ISWI ATPase SMARCA5.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24498324","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21900490","id":"PMC_21900490","title":"The chromatin remodeler ISWI regulates the cellular response to hypoxia: role of FIH.","date":"2011","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/21900490","citation_count":29,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22298509","id":"PMC_22298509","title":"Disparity in the DNA translocase domains of SWI/SNF and ISW2.","date":"2012","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/22298509","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12596906","id":"PMC_12596906","title":"Selective gene regulation by SWI/SNF-related chromatin remodeling factors.","date":"2003","source":"Current topics in microbiology and immunology","url":"https://pubmed.ncbi.nlm.nih.gov/12596906","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35129437","id":"PMC_35129437","title":"SWI/SNF senses carbon starvation with a pH-sensitive low-complexity sequence.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35129437","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24727082","id":"PMC_24727082","title":"Investigating the interactions of yeast prions: [SWI+], [PSI+], and [PIN+].","date":"2014","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24727082","citation_count":27,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24414837","id":"PMC_24414837","title":"Regulation of ISWI chromatin remodelling activity.","date":"2014","source":"Chromosoma","url":"https://pubmed.ncbi.nlm.nih.gov/24414837","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37119511","id":"PMC_37119511","title":"SWI/SNF Chromatin Remodelers: Structural, Functional and Mechanistic Implications.","date":"2023","source":"Cell biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/37119511","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33451916","id":"PMC_33451916","title":"SWI/SNF-deficient thoraco-pulmonary neoplasms.","date":"2021","source":"Seminars in diagnostic pathology","url":"https://pubmed.ncbi.nlm.nih.gov/33451916","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35911061","id":"PMC_35911061","title":"Emerging Themes in Mechanisms of Tumorigenesis by SWI/SNF Subunit Mutation.","date":"2022","source":"Epigenetics insights","url":"https://pubmed.ncbi.nlm.nih.gov/35911061","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37055726","id":"PMC_37055726","title":"The esBAF and ISWI nucleosome remodeling complexes influence occupancy of overlapping dinucleosomes and fragile nucleosomes in murine embryonic stem cells.","date":"2023","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/37055726","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"36354291","id":"PMC_36354291","title":"Paraspeckles interact with SWI/SNF subunit ARID1B to regulate transcription and splicing.","date":"2022","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/36354291","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28109157","id":"PMC_28109157","title":"Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail.","date":"2017","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/28109157","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"40269969","id":"PMC_40269969","title":"Chromatin remodeling and cancer: the critical influence of the SWI/SNF complex.","date":"2025","source":"Epigenetics & chromatin","url":"https://pubmed.ncbi.nlm.nih.gov/40269969","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17544291","id":"PMC_17544291","title":"ISWI chromatin remodeling in ovarian somatic and germ cells: revenge of the NURFs.","date":"2007","source":"Trends in endocrinology and metabolism: TEM","url":"https://pubmed.ncbi.nlm.nih.gov/17544291","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12477932","id":"PMC_12477932","title":"Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12477932","citation_count":1479,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26777405","id":"PMC_26777405","title":"ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure.","date":"2016","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26777405","citation_count":1233,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26186194","id":"PMC_26186194","title":"The BioPlex Network: A Systematic Exploration of the Human Interactome.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26186194","citation_count":1118,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"28514442","id":"PMC_28514442","title":"Architecture of the human interactome defines protein communities and disease networks.","date":"2017","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/28514442","citation_count":1085,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"16728976","id":"PMC_16728976","title":"A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling.","date":"2006","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/16728976","citation_count":918,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"29507755","id":"PMC_29507755","title":"VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation.","date":"2018","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/29507755","citation_count":829,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15772651","id":"PMC_15772651","title":"The DNA sequence of the human X chromosome.","date":"2005","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/15772651","citation_count":816,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14702039","id":"PMC_14702039","title":"Complete sequencing and characterization of 21,243 full-length human cDNAs.","date":"2003","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/14702039","citation_count":754,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"33961781","id":"PMC_33961781","title":"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.","date":"2021","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/33961781","citation_count":705,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"22939629","id":"PMC_22939629","title":"A census of human soluble protein complexes.","date":"2012","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/22939629","citation_count":689,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21873635","id":"PMC_21873635","title":"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium.","date":"2011","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/21873635","citation_count":656,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"20850016","id":"PMC_20850016","title":"Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers.","date":"2010","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/20850016","citation_count":639,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15489334","id":"PMC_15489334","title":"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).","date":"2004","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/15489334","citation_count":438,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"35271311","id":"PMC_35271311","title":"OpenCell: Endogenous tagging for the cartography of human cellular organization.","date":"2022","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/35271311","citation_count":432,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26344197","id":"PMC_26344197","title":"Panorama of ancient metazoan macromolecular complexes.","date":"2015","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/26344197","citation_count":407,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"34079125","id":"PMC_34079125","title":"A proximity-dependent biotinylation map of a human cell.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34079125","citation_count":339,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"30922402","id":"PMC_30922402","title":"Circular RNA circ-DONSON facilitates gastric cancer growth and invasion via NURF complex dependent activation of transcription factor SOX4.","date":"2019","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/30922402","citation_count":204,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"29568061","id":"PMC_29568061","title":"An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29568061","citation_count":201,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"11980720","id":"PMC_11980720","title":"WSTF-ISWI chromatin remodeling complex targets heterochromatic replication foci.","date":"2002","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/11980720","citation_count":194,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"22233809","id":"PMC_22233809","title":"Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer.","date":"2012","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/22233809","citation_count":185,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"25544563","id":"PMC_25544563","title":"Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes.","date":"2014","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/25544563","citation_count":173,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32807901","id":"PMC_32807901","title":"UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination.","date":"2020","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/32807901","citation_count":168,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14609955","id":"PMC_14609955","title":"Isolation of human NURF: a regulator of Engrailed gene expression.","date":"2003","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/14609955","citation_count":145,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"30554943","id":"PMC_30554943","title":"Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.","date":"2018","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/30554943","citation_count":136,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12112843","id":"PMC_12112843","title":"Identification of the phosphotyrosine proteome from thrombin activated platelets.","date":"2002","source":"Proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/12112843","citation_count":132,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"24457600","id":"PMC_24457600","title":"The central role of EED in the orchestration of polycomb group complexes.","date":"2014","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/24457600","citation_count":131,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"35140242","id":"PMC_35140242","title":"Human transcription factor protein interaction networks.","date":"2022","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/35140242","citation_count":123,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15640247","id":"PMC_15640247","title":"CECR2, a protein involved in neurulation, forms a novel chromatin remodeling complex with SNF2L.","date":"2005","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/15640247","citation_count":122,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"25609649","id":"PMC_25609649","title":"Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.","date":"2015","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/25609649","citation_count":120,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"30098595","id":"PMC_30098595","title":"LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3.","date":"2018","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/30098595","citation_count":115,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":40181,"output_tokens":3894,"usd":0.089477},"stage2":{"model":"claude-opus-4-6","input_tokens":7316,"output_tokens":3575,"usd":0.188933},"total_usd":0.548868,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":52415,"output_tokens":4509,"usd":0.11244},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":7229,"output_tokens":2768,"usd":0.158018}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"SMARCA1 (SNF2L) is implicated in neurodevelopmental disorders; the mammalian ISWI genes SMARCA1 and SMARCA5 encode the ATP-dependent chromatin remodeling proteins SNF2L and SNF2H, which interact with BAZ domain-containing proteins to generate eight distinct remodeling complexes involved in nucleosome positioning critical for neural progenitor-to-differentiated cell state transitions.\",\n      \"method\": \"Genetic studies and characterization of mice inactivated for ISWI and interacting proteins\",\n      \"journal\": \"Molecular and cellular neurosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic/KO studies in mice with defined cellular phenotype, single review summarizing multiple studies\",\n      \"pmids\": [\"29249292\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"A missense variant in SMARCA1 on the X chromosome segregates with psychotic disorders (schizophrenia spectrum) in a multiplex family, identifying SMARCA1 as a candidate causal gene for psychosis.\",\n      \"method\": \"Whole-genome sequencing in multiplex families with psychoses; variant segregation analysis\",\n      \"journal\": \"Molecular psychiatry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — genetic segregation only, no direct mechanistic/functional assay of SMARCA1 protein\",\n      \"pmids\": [\"27001614\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"SMARCA5 (SNF2H/ISWI isoform) and its binding partners ACF1 and WSTF are rapidly recruited to UV-C-induced DNA damage to facilitate CSB binding and promote transcription recovery after lesion-stalled transcription. SMARCA5 targeting to UV-C damage requires functional SWI2/SNF2-ATPase and SLIDE domains; after initial recruitment, SMARCA5 re-localizes away from the damage center requiring its HAND domain.\",\n      \"method\": \"Live cell imaging, domain mutagenesis, UV-C damage assays, transcription recovery assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — live imaging with domain-specific mutagenesis establishing functional requirements, single lab\",\n      \"pmids\": [\"24990377\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"An ACF1-ISWI (SNF2H/SMARCA5) chromatin-remodeling complex is required for DNA replication through heterochromatin in mammalian cells; ACF1 and SNF2H become specifically enriched in replicating pericentromeric heterochromatin, and RNAi depletion of ACF1 specifically impairs replication of pericentromeric heterochromatin and delays cell-cycle progression through late S phase.\",\n      \"method\": \"RNAi knockdown, cell fractionation, immunofluorescence co-localization with replication foci, cell cycle analysis\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (RNAi, localization, cell cycle), replicated with ACF1 mutant that cannot interact with SNF2H\",\n      \"pmids\": [\"12434153\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ISWI-class ACF1-SNF2H (SMARCA5) nucleosome remodeling is required for Artemis-dependent DSB repair in heterochromatin; ACF1-SNF2H requires RNF20 to bind heterochromatic DSBs, functions downstream of pKAP-1-mediated CHD3.1 dispersal, and counteracts CHD3.1 compaction activity to enable repair.\",\n      \"method\": \"Genetic epistasis, co-immunoprecipitation, knockdown with defined repair phenotype, live cell imaging\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — epistasis ordering plus reciprocal functional assays across multiple labs\",\n      \"pmids\": [\"25533843\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"ISWI (SMARCA5/SNF2H) depletion enhances HIF transcriptional activity without altering HIF protein levels; mechanistically, ISWI is required for full expression of the HIF hydroxylase FIH by altering RNA polymerase II loading at the FIH promoter, thereby indirectly suppressing HIF target gene expression.\",\n      \"method\": \"siRNA knockdown, reporter assays, ChIP for RNA Pol II, rescue experiments with exogenous FIH\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal assays (knockdown, ChIP, rescue), single lab\",\n      \"pmids\": [\"21900490\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"CTCF binding to target sites on DNA is facilitated by SMARCA5 (ISWI ATPase); SMARCA5 associates with the Cohesin complex, supports CTCF functionally at the ICR enhancer-blocking element, and together with CTCF and Cohesin is recruited to the SPI1 gene -14.4 Enhancer to regulate PU.1 expression in myeloid differentiation.\",\n      \"method\": \"ChIP, co-immunoprecipitation, knockdown, DNA methylation analysis (AZA treatment)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — multiple ChIP and co-IP experiments with functional readouts, single lab\",\n      \"pmids\": [\"24498324\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Smarca5 (Snf2h) is required for proliferation and differentiation of hematopoietic stem and progenitor cells; conditional deletion at onset of definitive hematopoiesis causes lethal anemia, blocks erythroid/myeloid maturation, and leads to increased p53 levels and activation (phosphorylation at S15, acetylation at K376), with p53 target activation and G2/M block in basophilic erythroblasts.\",\n      \"method\": \"Conditional knockout (Vav1-iCre and Epor-iCre), 4-OHT-mediated ex vivo deletion, FACS, Western blot\",\n      \"journal\": \"Stem cells (Dayton, Ohio)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean conditional KO with multiple orthogonal phenotypic readouts, replicated with two Cre lines\",\n      \"pmids\": [\"28276606\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Drosophila ISWI is acetylated at a single conserved lysine (K753) by the histone acetyltransferase GCN5, both in vivo and in vitro; the acetylated form of ISWI represents a minor species presumably associated with the NURF complex. The target sequence around K753 is similar to histone H3 around H3K14, explaining GCN5's dual substrate recognition.\",\n      \"method\": \"In vitro acetylation assay, mass spectrometry, in vivo labeling\",\n      \"journal\": \"BMC molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro enzymatic assay with in vivo confirmation, but Drosophila ortholog study\",\n      \"pmids\": [\"17760996\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"ISWI (Xenopus/Drosophila ortholog) is a RanGTP-dependent microtubule-associated protein required for chromosome segregation; recombinant ISWI induces MT nucleation, stabilization, and bundling in vitro; ISWI localizes to spindles during mitosis and is required for RanGTP-dependent MT stabilization during anaphase independently of its effect on chromosomes.\",\n      \"method\": \"Xenopus egg extract depletion, in vitro MT assay, live cell imaging in Drosophila S2 cells, immunolocalization\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vitro reconstitution plus depletion in egg extract and S2 cells, but Xenopus/Drosophila ortholog\",\n      \"pmids\": [\"20008562\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Each endogenously expressed ISWI ATPase (SNF2L/SMARCA1 and SNF2H/SMARCA5) co-purifies with every regulatory subunit, substantially increasing ISWI complex diversity; BAZ2B was identified as a novel seventh regulatory subunit. Reconstitution of catalytically active human ISWI complexes confirmed stable and direct interactions, and their nucleosome remodeling functions were profiled.\",\n      \"method\": \"Endogenous co-purification, reconstitution of active human ISWI complexes, nucleosome remodeling assays\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted catalytically active complexes with direct interaction confirmation, multiple orthogonal methods\",\n      \"pmids\": [\"28801535\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"H4K16 acetylation directly counteracts chromatin compaction mediated by the Drosophila ISWI ATPase; peptide competition assays revealed that H4K16 acetylation reduces the ability of ISWI to interact productively with its nucleosome substrate, and blocking H4K16 acetylation suppresses X chromosome defects caused by loss of ISWI function.\",\n      \"method\": \"Genetic epistasis (Drosophila), peptide competition assay, histone modification analysis\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro peptide competition plus genetic epistasis in Drosophila ortholog, multiple orthogonal approaches\",\n      \"pmids\": [\"11882543\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Crystal structure of Myceliophthora thermophila ISWI reveals that the N-terminal AutoN domain contains two inhibitory elements that bind the second RecA-like domain (core2) holding the enzyme in an inactive conformation; the H4 tail peptide binds core2 at a site overlapping one AutoN-binding site, explaining ISWI activation by H4; the C-terminal NegC domain binds core2 and functions as an allosteric element responding to extranucleosomal DNA length.\",\n      \"method\": \"Crystal structure determination, mutagenesis, ATPase and nucleosome remodeling assays\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure with functional mutagenesis validation, mechanistically complete\",\n      \"pmids\": [\"27919072\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Cryo-EM structures of yeast ISW1 (ISWI ortholog) in ADP-bound and ADP-BeFx-bound states reveal that after nucleosome binding, ISW1 is activated by substantial rearrangement of catalytic domains; the AutoN domain packs the first RecA-like core while NegC becomes disordered; local DNA distortion and translocation is induced without notable histone deformation, suggesting a common mechanism with Snf2.\",\n      \"method\": \"Cryo-EM structure determination at 3.3 Å, ATPase assays, crosslinking experiments\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — near-atomic cryo-EM with functional validation, includes human homolog activity comparison\",\n      \"pmids\": [\"30872815\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Loss of SNF2H (SMARCA5) in mammalian embryonic stem cells decreases nucleosomal phasing and increases linker lengths, providing in vivo evidence for ISWI function in nucleosomal spacing; SNF2H loss selectively impairs CTCF binding and disrupts chromosomal folding and insulation of topologically associated domains, whereas BRG1 loss specifically affects REST binding.\",\n      \"method\": \"Viable ESC knockout of SNF2H, MNase-seq, ATAC-seq, ChIP-seq, Hi-C\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with multiple genome-wide orthogonal readouts, strong mechanistic specificity shown\",\n      \"pmids\": [\"30996347\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The AutoN domain of ISWI does not act as a simple pseudosubstrate; the H4-tail binding pocket is adjacent to but not overlapping with the AutoN docking site. A third NTR motif (ppHSA) is functionally required in vivo and provides structural stability by clamping the NTR to Lobe 2 of the ATPase domain. A hitherto uncharacterized motif AcidicN cooperates with AutoN to confer H4-tail sensitivity.\",\n      \"method\": \"Mutagenesis, in vitro ATPase and nucleosome sliding assays, in vivo complementation, crosslinking\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — mutagenesis combined with in vitro reconstitution assays and in vivo functional rescue\",\n      \"pmids\": [\"28109157\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SMARCA1 (SNF2L) is an ISWI-family ATPase that pairs combinatorially with BAZ-domain regulatory subunits to form multiple distinct chromatin remodeling complexes; its catalytic activity is regulated by AutoN/AcidicN inhibitory domains antagonized by the histone H4 tail and extranucleosomal DNA, and by GCN5-mediated acetylation; SNF2L/SNF2H complexes mobilize nucleosomes to control nucleosomal spacing, transcription factor access, heterochromatin replication, and DNA damage repair, with SMARCA1 playing a specific role in neural progenitor differentiation and implicated in neurodevelopmental and psychotic disorders.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper and extract discoveries only from KEEP papers.\n\n**Classification Summary:**\n\nSMARCA1 encodes SNF2L, the catalytic ATPase subunit of the ISWI family (specifically the NURF complex in mammals), distinct from SNF2H (SMARCA5). Papers must be about this specific protein.\n\n**KEEP papers** (directly about SMARCA1/SNF2L or the NURF complex containing SNF2L):\n- PMID:27001614 — SMARCA1 missense variant in schizophrenia families\n- PMID:16728976 — PHD finger of NURF (BPTF) couples H3K4me3 to SNF2L/SMARCA1 recruitment\n- PMID:14609955 — Purification of human NURF containing SNF2L; neuronal role\n- PMID:15640247 — CECR2 forms complex with SNF2L (SMARCA1)\n- PMID:29249292 — SMARCA1 and SMARCA5 in brain development/NDDs (reviews SMARCA1 KO mice)\n- PMID:30922402 — circ-DONSON recruits NURF/SNF2L... EXCLUDE (alt-locus product/circRNA paper)\n- PMID:30098595 — DLEU1/SMARCA1/KPNA3 axis — KEEP (directly implicates SMARCA1 protein)\n- PMID:24990377 — SMARCA5 paper, not SMARCA1 — EXCLUDE (alias collision: describes SMARCA5/SNF2H)\n- PMID:17760996 — GCN5 acetylates Drosophila ISWI (ortholog) — KEEP\n- PMID:20008562 — Xenopus/Drosophila ISWI in chromosome segregation — KEEP (ortholog)\n- PMID:11882543 — Drosophila ISWI modulation by H4K16ac — KEEP (ortholog)\n- PMID:23143334 — ISWI regulation by AutoN/NegC (Drosophila) — KEEP (ortholog)\n- PMID:27919072 — Crystal structure of ISWI (fungal ortholog) — KEEP (ortholog, Tier 1)\n- PMID:30872815 — Cryo-EM of yeast ISW1 (ortholog) — KEEP\n- PMID:28109157 — ISWI AutoN/AcidicN/ppHSA regulation — KEEP (ortholog)\n- PMID:21900490 — ISWI regulates FIH/hypoxia response — need to check: says \"ISWI\" in mammalian cells broadly, not specific to SMARCA1 — borderline, but mechanistic about ISWI family; EXCLUDE (not specific to SMARCA1)\n- PMID:30996347 — SNF2H (SMARCA5) paper — EXCLUDE\n- PMID:12434153 — ACF1-SNF2H (SMARCA5) — EXCLUDE\n- PMID:9730600 — Cloning of SMARCA5/hSNF2H — EXCLUDE\n- PMID:28801535 — Expansion of ISWI complexes with SNF2H/SNF2L; both ATPases — KEEP (includes SNF2L/SMARCA1)\n- PMID:12477932, 14702039, etc. — cDNA/genome sequencing projects — EXCLUDE (no mechanistic findings)\n- PMID:26186194, 28514442, 33961781 — BioPlex interactomes — EXCLUDE (proteomics, no specific mechanism)\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"The PHD finger of BPTF (the large subunit of the NURF complex) directly binds trimethylated histone H3 lysine 4 (H3K4me3), coupling this epigenetic mark to recruitment of the associated ATPase SNF2L (SMARCA1) to target promoters such as HOXC8. Depletion of H3K4me3 causes partial release of BPTF from chromatin and defective recruitment of SNF2L, and loss of BPTF in Xenopus embryos compromises spatial control of Hox gene expression.\",\n      \"method\": \"Peptide pulldown, ChIP, Xenopus loss-of-function, co-immunoprecipitation\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, ChIP, in vivo loss-of-function in Xenopus, multiple orthogonal methods in one study\",\n      \"pmids\": [\"16728976\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Human SNF2L (SMARCA1) was purified as the ATPase catalytic subunit of a human NURF complex (hNURF) orthologous to Drosophila NURF. hNURF is enriched in brain tissue and directly regulates expression of the homeodomain protein Engrailed, potentiating neurite outgrowth in cell culture.\",\n      \"method\": \"Biochemical purification, immunoprecipitation, reporter gene assays, neurite outgrowth assay\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — purification to homogeneity, functional validation in cell culture, brain-enriched expression confirmed\",\n      \"pmids\": [\"14609955\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"SNF2L (SMARCA1) forms a novel heterodimeric chromatin remodeling complex (CERF) with CECR2, a bromodomain- and DDT-domain-containing protein. CERF remodels chromatin in vitro and has nucleosome-stimulated ATPase activity. Loss of Cecr2 in mice causes exencephaly (neural tube defect), implicating SNF2L-containing CERF in neurulation.\",\n      \"method\": \"Biochemical co-purification, in vitro chromatin remodeling assay, ATPase assay, mouse genetrap knockout\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro reconstitution of complex activity, murine loss-of-function with clear developmental phenotype\",\n      \"pmids\": [\"15640247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Drosophila ISWI (ortholog of SMARCA1) activity is negatively regulated by acetylation of histone H4 at lysine 16 (H4K16ac). H4K16 acetylation reduces ISWI's ability to interact productively with its nucleosome substrate, as shown by peptide competition assays; blocking H4K16ac suppresses X-chromosome defects from ISWI loss, while forced H4K16ac in ISWI mutant females phenocopies ISWI mutant males.\",\n      \"method\": \"Drosophila genetics (epistasis), peptide competition ATPase assay, MOF overexpression\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis in Drosophila corroborated by biochemical peptide competition, replicated with multiple alleles\",\n      \"pmids\": [\"11882543\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The histone acetyltransferase GCN5 acetylates Drosophila ISWI (ortholog of SMARCA1) at a single conserved lysine (K753) in vivo and in vitro. The target sequence is similar to the N-terminus of histone H3 where GCN5 acetylates H3K14. Acetylated ISWI represents a minor species associated with the NURF complex.\",\n      \"method\": \"In vitro acetyltransferase assay, mass spectrometry, in vivo acetylation detection\",\n      \"journal\": \"BMC molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro assay with identification of specific site, but single study with limited functional follow-up\",\n      \"pmids\": [\"17760996\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Xenopus/Drosophila ISWI (ortholog of SMARCA1) is a RanGTP-dependent microtubule-associated protein required for chromosome segregation. Recombinant ISWI induces MT nucleation, stabilization, and bundling in vitro. Depletion in Xenopus egg extracts leads to spindle MT disappearance and failed chromosome segregation in anaphase; depletion in Drosophila S2 cells causes spindle defects and growth arrest. ISWI localizes to spindles during mitosis, distinct from its interphase chromatin role.\",\n      \"method\": \"Xenopus egg extract depletion, in vitro MT assembly assay, RNAi in Drosophila S2 cells, live imaging\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro reconstitution of MT activities, loss-of-function in two model systems with clear mitotic phenotype\",\n      \"pmids\": [\"20008562\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"ISWI (ortholog of SMARCA1) is regulated by two conserved inhibitory domains: AutoN (inhibits ATP hydrolysis) and NegC (uncouples ATP hydrolysis from productive DNA translocation). The H4 basic patch on nucleosomes antagonizes AutoN, and extranucleosomal DNA antagonizes NegC, enabling remodeling only on appropriate chromatin substrates. Mutation or removal of AutoN and NegC confers SWI/SNF-like biochemical attributes on ISWI.\",\n      \"method\": \"ATPase assays, nucleosome sliding assays, domain deletion/mutagenesis in Drosophila ISWI\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted in vitro with mutagenesis, multiple functional assays, mechanistic model validated\",\n      \"pmids\": [\"23143334\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Crystal structures of ISWI from thermophilic yeast Myceliophthora thermophila reveal that the AutoN domain contains two inhibitory elements that bind the second RecA-like domain (core2), holding ISWI in an inactive conformation. The histone H4 peptide binds to core2 at a site coincident with one AutoN-binding site, explaining H4-tail-dependent activation. The NegC domain contacts core2 as an allosteric element responding to extranucleosomal DNA length.\",\n      \"method\": \"X-ray crystallography, structure-function mutagenesis, peptide binding assays\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — atomic-resolution crystal structure with functional mutagenesis validation\",\n      \"pmids\": [\"27919072\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Cryo-EM structures of yeast ISW1 (ISWI ortholog of SMARCA1) in ADP-bound and ADP-BeFx-bound states show that nucleosome binding activates ISW1 via substantial rearrangement of catalytic domains. The AutoN domain packs against the first RecA-like core and NegC becomes disordered upon activation. Local DNA distortion and translocation occurs without notable histone deformation, suggesting a general mechanism of chromatin remodeling involving DNA distortion independent of histone displacement.\",\n      \"method\": \"Cryo-EM at 3.3 Å resolution, crosslinking assays to prevent histone distortion\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — near-atomic cryo-EM structure with mechanistic functional validation\",\n      \"pmids\": [\"30872815\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Mapping of the H4-tail binding pocket of ISWI (ortholog of SMARCA1) reveals that AutoN does not act as a simple pseudosubstrate competing with H4. Instead, AutoN cooperates with a second motif (AcidicN) to confer H4-tail sensitivity and discriminate nucleosomes from free DNA. A third N-terminal region motif (ppHSA) stabilizes the NTR by clamping it to Lobe 2 of the ATPase domain and is required in vivo.\",\n      \"method\": \"Mutagenesis, in vitro ATPase and sliding assays, cross-linking, in vivo complementation in Drosophila\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — mutagenesis combined with in vitro reconstitution and in vivo validation\",\n      \"pmids\": [\"28109157\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Each endogenously expressed ISWI ATPase (including SNF2L/SMARCA1) co-purifies with every regulatory subunit, substantially expanding the diversity of ISWI complexes beyond previously known pairings. SNF2L forms stable, direct complexes with all tested regulatory subunits. BAZ2B was identified as a novel seventh regulatory subunit. Reconstituted human ISWI complexes containing SNF2L showed nucleosome remodeling activity.\",\n      \"method\": \"Endogenous co-purification, reconstitution of catalytically active complexes, nucleosome remodeling assays\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reconstitution with functional validation, but SNF2L-specific functional data not distinguished from SNF2H in all assays\",\n      \"pmids\": [\"28801535\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Whole-genome sequencing of multiplex families with psychotic disorders identified a novel private missense variant in SMARCA1 (on the X chromosome) segregating with illness in four affected siblings and their unaffected mother. The variant alters the SMARCA1 protein sequence and is considered a candidate causal mutation for schizophrenia spectrum disorders in this family.\",\n      \"method\": \"Whole-genome sequencing, familial segregation analysis\",\n      \"journal\": \"Molecular psychiatry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 — genetic association without experimental functional validation of the variant's effect on SMARCA1 protein\",\n      \"pmids\": [\"27001614\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"LncRNA DLEU1 promotes colorectal cancer progression by recruiting SMARCA1 (SNF2L, a subunit of the NURF chromatin remodeling complex) to the promoter of KPNA3, activating its transcription. Biotin-coupled probe pulldown, RNA immunoprecipitation, and FISH confirmed direct interaction between DLEU1 and SMARCA1. DLEU1 knockdown reduced SMARCA1 deposition at the KPNA3 promoter.\",\n      \"method\": \"RNA immunoprecipitation, biotin-probe pulldown, ChIP, FISH, shRNA knockdown with phenotypic rescue\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — multiple biochemical methods confirm DLEU1-SMARCA1 interaction and promoter recruitment, but mechanistic dissection is limited\",\n      \"pmids\": [\"30098595\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Review and genetic analysis of Smarca1 knockout mice establishes that SMARCA1 (SNF2L) is required for proper brain development. Loss of SMARCA1 function has been implicated in neurodevelopmental disorders, and ISWI complex-mediated nucleosome positioning within gene regulatory elements is important for the transition from committed neural progenitor states to differentiated cell states.\",\n      \"method\": \"Mouse knockout analysis, genetic studies\",\n      \"journal\": \"Molecular and cellular neurosciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — review summarizing mouse KO phenotypes without primary mechanistic data in this paper\",\n      \"pmids\": [\"29249292\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SMARCA1 (SNF2L) is the catalytic ATPase subunit of the mammalian NURF and CERF chromatin remodeling complexes; it is recruited to H3K4me3-marked chromatin via the BPTF PHD finger, remodels nucleosomes through an ATP-dependent DNA translocation mechanism regulated by inhibitory AutoN and NegC domains that are antagonized by the histone H4 tail and extranucleosomal DNA respectively, and functions beyond chromatin remodeling as a RanGTP-dependent microtubule-associated protein required for anaphase chromosome segregation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SMARCA1 (SNF2L) is an ISWI-family ATP-dependent chromatin remodeling ATPase that, together with its paralog SMARCA5 (SNF2H), combinatorially associates with BAZ-domain regulatory subunits to form multiple distinct nucleosome-remodeling complexes that control nucleosome spacing, transcription factor access, heterochromatin replication, and DNA damage repair [PMID:28801535, PMID:30996347, PMID:12434153, PMID:25533843]. Its catalytic activity is autoinhibited by N-terminal AutoN and AcidicN domains that dock onto the second RecA-like lobe; activation requires displacement of these elements by the histone H4 tail, while the C-terminal NegC domain allosterically senses extranucleosomal DNA length, together coupling ATPase firing to proper nucleosomal substrate recognition [PMID:27919072, PMID:28109157, PMID:30872815]. SMARCA1 plays a specific role in neural progenitor differentiation, and a missense variant on the X chromosome segregates with psychotic illness in a multiplex family [PMID:29249292, PMID:27001614]. ISWI-mediated nucleosome remodeling additionally facilitates CTCF binding and chromosomal domain insulation, supports transcription-coupled DNA repair, and is regulated by GCN5-mediated acetylation and H4K16 acetylation status [PMID:30996347, PMID:24990377, PMID:17760996, PMID:11882543].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Establishing that H4K16 acetylation directly antagonizes ISWI remodeling resolved how a single histone mark could counter ISWI-mediated chromatin compaction and explained dosage compensation phenotypes on the Drosophila X chromosome.\",\n      \"evidence\": \"Peptide competition assays and genetic epistasis in Drosophila\",\n      \"pmids\": [\"11882543\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether H4K16ac regulation applies identically to mammalian SNF2L versus SNF2H\", \"No structural basis for how H4K16ac prevents productive substrate engagement at this time\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Demonstrating that the ACF1–SNF2H complex is specifically required for replication through pericentromeric heterochromatin established a direct role for ISWI remodeling in DNA replication beyond transcription.\",\n      \"evidence\": \"RNAi knockdown of ACF1, immunofluorescence co-localization with replication foci, and cell cycle analysis in mammalian cells\",\n      \"pmids\": [\"12434153\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether SNF2L/SMARCA1 can substitute for SNF2H in heterochromatin replication\", \"Mechanism by which nucleosome remodeling facilitates replication fork progression\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identifying GCN5-mediated acetylation of a conserved ISWI lysine revealed a post-translational regulatory input on the remodeler itself, analogous to histone modification.\",\n      \"evidence\": \"In vitro acetylation assay, mass spectrometry, and in vivo labeling in Drosophila\",\n      \"pmids\": [\"17760996\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of K753 acetylation on ATPase or remodeling activity not determined\", \"Whether mammalian SNF2L is acetylated at the equivalent site\", \"Stoichiometry of acetylated ISWI in vivo unclear\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Discovering that ISWI functions as a RanGTP-dependent microtubule-associated protein required for spindle assembly revealed an unexpected chromatin-independent mitotic role.\",\n      \"evidence\": \"Xenopus egg extract depletion, in vitro MT nucleation/bundling assays, live imaging in Drosophila S2 cells\",\n      \"pmids\": [\"20008562\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No evidence this MT function is conserved for mammalian SMARCA1\", \"Structural basis for MT binding versus nucleosome binding unknown\", \"Relative contribution to mitotic fidelity versus chromatin remodeling not separated\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showing that ISWI/SNF2H controls HIF transcriptional output by regulating RNA Pol II loading at the FIH promoter linked nucleosome remodeling to hypoxia signaling.\",\n      \"evidence\": \"siRNA knockdown, luciferase reporter assays, ChIP for Pol II, and rescue with exogenous FIH\",\n      \"pmids\": [\"21900490\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether SNF2L contributes to FIH regulation or this is SNF2H-specific\", \"No genome-wide assessment of ISWI-dependent promoter remodeling at this time\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"A set of studies established that ISWI complexes operate in DNA damage repair — ACF1–SNF2H is required for Artemis-dependent DSB repair in heterochromatin and for transcription-coupled repair after UV damage — positioning ISWI as a chromatin access factor for multiple repair pathways.\",\n      \"evidence\": \"Epistasis ordering of ACF1–SNF2H downstream of pKAP-1/CHD3.1 dispersal at DSBs; live-cell imaging and domain mutagenesis for UV-C recruitment of SNF2H\",\n      \"pmids\": [\"25533843\", \"24990377\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether SNF2L/SMARCA1 participates in any DNA repair pathway\", \"Mechanism by which RNF20 recruits ACF1–SNF2H to heterochromatic DSBs at the structural level\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connecting SMARCA5 to CTCF binding and cohesin association at regulatory elements extended ISWI function to insulator activity and myeloid differentiation, while concurrent work implicated SMARCA1 specifically in neurodevelopmental progenitor transitions.\",\n      \"evidence\": \"ChIP, co-IP, knockdown, and DNA methylation analysis for CTCF/cohesin; genetic KO studies in mice for neurodevelopmental role\",\n      \"pmids\": [\"24498324\", \"29249292\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct comparison of SNF2L versus SNF2H contribution to CTCF-dependent insulation\", \"Mechanism linking SMARCA1 to neural progenitor differentiation not molecularly defined\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The crystal structure of a fungal ISWI resolved how the AutoN and NegC inhibitory domains hold the ATPase inactive and how the H4 tail activates it by competing for the same surface on RecA lobe 2, providing the first structural framework for ISWI regulation.\",\n      \"evidence\": \"Crystal structure of M. thermophila ISWI with mutagenesis and ATPase/remodeling assays\",\n      \"pmids\": [\"27919072\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure was of a fungal ortholog; mammalian SNF2L-specific structural details unknown\", \"NegC-extranucleosomal DNA sensing mechanism not structurally visualized\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Refinement of the autoinhibition model revealed that AutoN and the H4-tail binding pocket are adjacent but not overlapping, and identified AcidicN and ppHSA as additional functional motifs, establishing a multi-element regulatory switch rather than simple pseudosubstrate inhibition.\",\n      \"evidence\": \"Systematic mutagenesis with in vitro ATPase/sliding assays and in vivo complementation in Drosophila\",\n      \"pmids\": [\"28109157\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How AcidicN cooperates with AutoN at the atomic level not resolved\", \"Whether mammalian SNF2L and SNF2H differ in AutoN/AcidicN regulation\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Endogenous purification showed that each ISWI ATPase (SNF2L and SNF2H) can pair with every known regulatory subunit, dramatically expanding the combinatorial complexity of ISWI complexes beyond the originally described pairings, and identified BAZ2B as a novel seventh subunit.\",\n      \"evidence\": \"Endogenous co-purification, reconstitution of catalytically active human ISWI complexes, and nucleosome remodeling assays\",\n      \"pmids\": [\"28801535\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional specialization of each SNF2L-containing complex not individually characterized\", \"Tissue-specific expression and regulation of complex assembly unknown\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Conditional knockout of Smarca5 in hematopoietic cells demonstrated that SNF2H is essential for erythroid/myeloid maturation via p53-dependent cell cycle arrest, linking ISWI remodeling to proliferation control in blood development.\",\n      \"evidence\": \"Conditional KO with Vav1-iCre and Epor-iCre, FACS, Western blot for p53 activation\",\n      \"pmids\": [\"28276606\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether SNF2L/SMARCA1 has a compensatory or distinct role in hematopoiesis not tested\", \"Direct versus indirect mechanism of p53 activation upon SNF2H loss unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Cryo-EM structures of nucleosome-bound ISW1 captured the activated state, revealing large-scale rearrangement of catalytic domains upon nucleosome engagement and local DNA distortion without histone deformation, establishing the translocation mechanism shared with SWI/SNF remodelers.\",\n      \"evidence\": \"Cryo-EM at 3.3 Å resolution of yeast ISW1 with ADP and ADP-BeFx, crosslinking, ATPase assays\",\n      \"pmids\": [\"30872815\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structures are of yeast ISW1; mammalian SMARCA1-specific complex structures not available\", \"Mechanism of multi-nucleosome spacing (ruler model) not structurally visualized\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Genome-wide analysis in ESCs showed that SNF2H loss decreases nucleosome phasing, increases linker length, and specifically impairs CTCF binding and TAD insulation, providing the first in vivo evidence that ISWI is the primary spacing enzyme and a determinant of 3D genome architecture.\",\n      \"evidence\": \"SNF2H knockout ESCs analyzed by MNase-seq, ATAC-seq, ChIP-seq, and Hi-C\",\n      \"pmids\": [\"30996347\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Analogous genome-wide studies for SNF2L/SMARCA1 loss not performed\", \"Whether SNF2L and SNF2H have redundant or distinct spacing activities in vivo\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific non-redundant functions of SMARCA1 (SNF2L) versus SMARCA5 (SNF2H) remain poorly resolved: most mechanistic and structural work has been performed on SNF2H or non-mammalian orthologs, leaving SNF2L-specific complex functions, tissue-specific roles beyond neural progenitors, and whether SNF2L contributes independently to genome architecture largely uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No SMARCA1-specific conditional KO phenotype in mammalian systems reported\", \"No genome-wide nucleosome spacing or CTCF binding data specific to SMARCA1 loss\", \"Structural basis for any functional divergence between SNF2L and SNF2H unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [10, 12, 13, 15]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [11, 12, 15]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 3, 7, 14]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [3, 4, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [10, 11, 12, 14, 15]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"R-HSA-69306\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [5, 6, 14]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [0, 7]}\n    ],\n    \"complexes\": [\n      \"ACF complex\",\n      \"NURF complex\",\n      \"CHRAC complex\",\n      \"WICH complex\"\n    ],\n    \"partners\": [\n      \"SMARCA5\",\n      \"BAZ1A\",\n      \"BAZ1B\",\n      \"BAZ2A\",\n      \"BAZ2B\",\n      \"BPTF\",\n      \"RSF1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"SMARCA1 (SNF2L) is the catalytic ATPase subunit of multiple ISWI-family chromatin remodeling complexes—including NURF and CERF—that reposition nucleosomes to regulate gene expression during neural development and other processes [PMID:14609955, PMID:15640247, PMID:28801535]. Its remodeling activity is gated by two conserved autoinhibitory domains, AutoN and NegC, which restrict ATP hydrolysis and productive DNA translocation, respectively; these are relieved by the histone H4 basic patch and extranucleosomal DNA, ensuring substrate-specific activation [PMID:23143334, PMID:27919072, PMID:30872815]. SMARCA1 is recruited to H3K4me3-marked chromatin via the PHD finger of its NURF partner BPTF and can also be guided to specific promoters by lncRNAs such as DLEU1 [PMID:16728976, PMID:30098595]. Beyond its chromatin role, the ISWI ortholog functions as a RanGTP-dependent microtubule-associated protein required for spindle integrity and anaphase chromosome segregation [PMID:20008562].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Establishing how the nucleosome substrate regulates ISWI activity: H4K16 acetylation was shown to antagonize ISWI function, revealing that the unmodified H4 tail is a critical activating signal for the ATPase.\",\n      \"evidence\": \"Drosophila genetic epistasis combined with peptide competition ATPase assays\",\n      \"pmids\": [\"11882543\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the H4K16ac effect is direct on the mammalian SNF2L enzyme was not tested\", \"The structural basis for H4-tail recognition was unknown\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Identifying the biological context of mammalian SMARCA1: purification of human NURF (hNURF) established SNF2L as its ATPase subunit, showed enrichment in brain, and linked the complex to Engrailed-dependent neurite outgrowth.\",\n      \"evidence\": \"Biochemical purification, reporter assays, and neurite outgrowth in cultured cells\",\n      \"pmids\": [\"14609955\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo requirement for hNURF in mammalian brain development was not demonstrated\", \"How SNF2L is targeted to Engrailed regulatory elements was unclear\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Expanding the repertoire of SMARCA1 complexes: discovery of CERF (CECR2–SNF2L) demonstrated that SMARCA1 functions in a second remodeling complex, and Cecr2 knockout mice linked this complex to neurulation.\",\n      \"evidence\": \"Co-purification, in vitro remodeling assays, and mouse genetrap knockout causing exencephaly\",\n      \"pmids\": [\"15640247\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether CERF has distinct genomic targets from NURF was unknown\", \"The contribution of SNF2L catalytic activity versus CECR2 scaffolding was not dissected\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Determining how SMARCA1 is targeted to active chromatin: the PHD finger of BPTF was shown to read H3K4me3, coupling this epigenetic mark to NURF/SNF2L recruitment at Hox gene promoters.\",\n      \"evidence\": \"Peptide pulldown, ChIP, and Xenopus loss-of-function\",\n      \"pmids\": [\"16728976\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether H3K4me3-directed recruitment is the sole targeting mechanism for SNF2L was not resolved\", \"Mammalian in vivo validation was lacking\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Revealing a non-chromatin function: ISWI/SMARCA1 ortholog was identified as a RanGTP-dependent microtubule-associated protein that nucleates and bundles microtubules, with depletion causing spindle collapse and failed anaphase chromosome segregation.\",\n      \"evidence\": \"In vitro MT assembly reconstitution, Xenopus egg extract depletion, Drosophila S2 cell RNAi, and live imaging\",\n      \"pmids\": [\"20008562\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether mammalian SMARCA1 retains the mitotic MT function was not shown\", \"The relationship between chromatin remodeling and MT-stabilizing activities is unresolved\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Defining the autoinhibitory mechanism: two conserved domains (AutoN and NegC) were shown to suppress ATPase activity and productive DNA translocation, respectively, and are antagonized by the H4 basic patch and extranucleosomal DNA—explaining why ISWI remodels only appropriate nucleosomal substrates.\",\n      \"evidence\": \"Domain deletion/mutagenesis with in vitro ATPase and nucleosome sliding assays on Drosophila ISWI\",\n      \"pmids\": [\"23143334\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis for AutoN and NegC inhibition was not yet available\", \"Whether human SNF2L autoinhibition follows identical rules was assumed but not directly tested\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Providing the structural basis for autoinhibition and H4-tail activation: crystal structures revealed that AutoN binds RecA-like core2 to lock ISWI in an inactive state, and the H4 tail competes at an overlapping binding site to relieve inhibition.\",\n      \"evidence\": \"X-ray crystallography of M. thermophila ISWI with structure-function mutagenesis\",\n      \"pmids\": [\"27919072\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full nucleosome-bound structure was not obtained\", \"NegC relief mechanism upon extranucleosomal DNA sensing lacked atomic detail\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Refining the N-terminal regulatory region: AutoN was shown not to be a simple pseudosubstrate; instead it cooperates with AcidicN and ppHSA motifs to confer H4-tail sensitivity and discriminate nucleosomes from free DNA, with ppHSA required in vivo.\",\n      \"evidence\": \"Mutagenesis, in vitro ATPase/sliding assays, cross-linking, Drosophila in vivo complementation\",\n      \"pmids\": [\"28109157\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How AcidicN and ppHSA are affected by post-translational modifications is unknown\", \"Whether regulatory subunits modulate AutoN/NegC gating was not addressed\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Expanding ISWI complex combinatorics: endogenous co-purification showed SNF2L can pair with every known ISWI regulatory subunit (including a novel partner BAZ2B), vastly increasing the diversity of SMARCA1-containing complexes.\",\n      \"evidence\": \"Endogenous co-purification and reconstitution of active complexes with nucleosome remodeling assays\",\n      \"pmids\": [\"28801535\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional specificity of each SNF2L-containing complex was not distinguished\", \"In vivo relevance of BAZ2B–SNF2L pairing was not established\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Visualizing the remodeling mechanism at near-atomic resolution: cryo-EM structures of nucleosome-bound ISW1 revealed that substrate binding triggers major rearrangement of catalytic domains with AutoN repacking and NegC disordering, and that DNA is translocated with local distortion but without notable histone deformation.\",\n      \"evidence\": \"Cryo-EM at 3.3 Å resolution with crosslinking-based functional validation\",\n      \"pmids\": [\"30872815\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structures of mammalian SNF2L on nucleosomes are still lacking\", \"Transition-state intermediates during the full translocation cycle were not captured\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include: the genomic target specificity and non-redundancy of each SMARCA1-containing complex in mammalian tissues; whether the mitotic microtubule function of SMARCA1 is conserved and physiologically relevant in mammals; and the mechanistic contribution of SMARCA1 variants to neurodevelopmental and psychiatric disease.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No mammalian conditional knockout systematically comparing complex-specific phenotypes\", \"Mitotic MT role not tested in mammalian cells\", \"Disease-linked SMARCA1 variants lack functional validation\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [1, 2, 6, 7, 8, 9]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [6, 8]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [3, 6, 7, 9]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1, 12]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 1, 2, 6, 8, 10]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1, 12]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 2, 13]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [\n      \"NURF\",\n      \"CERF\"\n    ],\n    \"partners\": [\n      \"BPTF\",\n      \"CECR2\",\n      \"BAZ2B\",\n      \"DLEU1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}