{"gene":"SGF29","run_date":"2026-06-10T07:46:31","timeline":{"discoveries":[{"year":2011,"finding":"Crystal structures of the tandem Tudor domains of S. cerevisiae and human SGF29 bound to H3K4me2 and H3K4me3 peptides revealed that the two Tudor domains pack face-to-face, with one pocket accommodating the H3A1 residue and the other the methylated K4 residue. The limited cleft length between the two pockets confers selectivity for H3K4me2/3. In vitro and in vivo functional assays demonstrated that H3K4me2/3 recognition by SGF29 is required for SAGA complex recruitment to target gene loci and consequent histone H3 acetylation.","method":"Crystal structure (X-ray crystallography), peptide binding assays, in vivo ChIP and histone acetylation assays, mutagenesis of binding pockets","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structures at ~2 Å with mutagenesis and orthogonal in vitro/in vivo functional validation in a single rigorous study","pmids":["21685874"],"is_preprint":false},{"year":2010,"finding":"The tandem Tudor domain at the C-terminus of S. cerevisiae Sgf29 was successfully crystallized and diffracted to 1.92 Å resolution, confirming the domain adopts a distinct structural fold amenable to high-resolution analysis.","method":"X-ray crystallography (preliminary crystallographic analysis)","journal":"Acta crystallographica. Section F, Structural biology and crystallization communications","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — structural data from a single crystallographic report with no functional follow-up in this paper","pmids":["20693663"],"is_preprint":false},{"year":2007,"finding":"Rat SGF29 directly interacted with rADA3 (direct interaction) and co-immunoprecipitated with rGCN5 and rSPT3, establishing it as a component of the TFTC/STAGA complexes. SGF29 was recruited to c-Myc target gene promoters together with c-Myc and activated c-Myc target gene expression. Knockdown of rSGF29 suppressed c-Myc target gene expression and inhibited anchorage-independent growth, tumorigenicity, and lung metastasis.","method":"Co-immunoprecipitation, ChIP, gene expression assays, siRNA knockdown, in vivo tumor xenograft assay","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP with multiple subunits, ChIP, and functional KD phenotype; single lab, multiple orthogonal methods","pmids":["17334388"],"is_preprint":false},{"year":2013,"finding":"Human SGF29 is a subunit of both the SAGA and ATAC histone acetyltransferase/co-activator complexes. SGF29 knockdown impaired transcription of ER stress genes GRP78 and CHOP, and reduced H3K14 acetylation at these loci. Additionally, SGF29 was required for maintenance of H3K4me3 at these promoters prior to ER stress; reduced H3K4me3 in SGF29-depleted cells correlated with decreased association of ASH2L (a core SET1/MLL complex component) at these gene loci, indicating a role for SGF29 in coordinating both H3K4me3 maintenance and H3K14 acetylation.","method":"siRNA knockdown, ChIP, quantitative RT-PCR, mass spectrometry-based complex identification","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD with multiple chromatin readouts (ChIP for H3K4me3, H3K14ac, and ASH2L binding) in a single lab","pmids":["23894581"],"is_preprint":false},{"year":2013,"finding":"In S. cerevisiae, domain analysis identified two minimal boundary-forming regions in Sgf29: the N-terminal region (aa 1–12) and the Tudor domain-containing C-terminal region (aa 110–255). Critically, the boundary formation activity of these minimal regions was shown to be independent of Gcn5 acetyltransferase activity, and in vivo analysis showed Sgf29 and Gcn5 perform distinct functions at native telomere boundary regions.","method":"Yeast genetic boundary assay, domain deletion/truncation analysis, in vivo telomere boundary assay","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain truncation with epistasis analysis (Gcn5-independent boundary function), single lab","pmids":["24307402"],"is_preprint":false},{"year":2023,"finding":"SGF29 forms liquid-like nuclear condensates during cellular senescence in human mesenchymal progenitor cells and fibroblasts via phase separation. Arg207 within the intrinsically disordered region is the key residue for condensate formation. Both condensate formation and H3K4me3 binding are required for SGF29 to establish its chromatin localization, recruit transcription factors and co-activators to specific genomic loci, and activate senescence-associated genes including CDKN1A. Condensate formation alone is not sufficient for H3K4me3 binding or transactivation.","method":"Mutagenesis (R207 mutation), live-cell imaging of phase separation, ChIP-seq, ATAC-seq, RNA-seq, co-activator recruitment assays","journal":"Cell discovery","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis of key IDR residue with orthogonal epigenomic and transcriptomic validation; single lab","pmids":["37935676"],"is_preprint":false},{"year":2024,"finding":"CRISPR-Cas9 domain-focused screen identified SGF29 as required for transcription of AML oncogenes including MEIS1. SGF29 deletion impaired leukemogenesis across multiple AML subtype models, establishing the SGF29 Tudor domain (H3K4me3 reader function) as a nononcogenic dependency in AML.","method":"CRISPR-Cas9 domain-focused library screen, CRISPR droplet sequencing, in vivo leukemia models","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic CRISPR screen with in vivo functional validation in multiple AML models; single lab","pmids":["38048593"],"is_preprint":false},{"year":2026,"finding":"In mouse ESCs, Sgf29 knockout reduced H3K9ac and chromatin accessibility at promoters and enhancers of pluripotency genes, triggering differentiation. Sgf29 was shown to interact with Oct4 and Nanog (but not Sox2) to co-regulate pluripotency gene expression. Sgf29 KO reduced Oct4 binding to Nanog and Klf4 loci. Sgf29 knockdown in pre-implantation embryos reduced blastocyst rate and decreased H3K9ac, with aberrant Oct4 and Nanog expression.","method":"Knockout/knockdown in mESCs, co-immunoprecipitation (Sgf29 with Oct4/Nanog), ChIP-seq for H3K9ac and transcription factor binding, ATAC-seq, pre-implantation embryo assays","journal":"Science China. Life sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO + Co-IP + ChIP-seq + ATAC-seq with multiple orthogonal readouts; single lab","pmids":["41843375"],"is_preprint":false},{"year":2024,"finding":"A high-throughput imaging-based CRISPR screen (TAILS) identified SGF29 as a promoter of the Alternative Lengthening of Telomeres (ALT) pathway, placing SGF29 functionally in telomere maintenance via recombination.","method":"High-throughput CRISPR screen with native FISH-based optical readout (TAILS)","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single screening hit from a preprint, no mechanistic follow-up on SGF29 specifically in this paper","pmids":["bio_10.1101_2024.11.15.623791"],"is_preprint":true}],"current_model":"SGF29 is a subunit of the SAGA (and related ATAC) transcriptional co-activator complex that uses its tandem Tudor domains to selectively bind H3K4me2/3 histone marks—through a structurally defined dual-pocket mechanism—thereby recruiting the SAGA complex to active promoters and promoting GCN5-mediated histone H3 acetylation; it additionally forms phase-separated nuclear condensates (via Arg207 in its IDR) during senescence to reinforce transcription of senescence genes, interacts with Oct4 and Nanog to maintain pluripotency chromatin accessibility, and is required for expression of AML oncogenes and leukemogenesis, making its Tudor domain an emerging therapeutic target."},"narrative":{"mechanistic_narrative":"SGF29 is a histone-mark reader subunit of the SAGA and ATAC histone acetyltransferase/co-activator complexes that couples recognition of active-promoter chromatin to GCN5-family histone acetylation [PMID:21685874, PMID:23894581]. Its tandem Tudor domains pack face-to-face to form a dual-pocket cleft in which one pocket binds the H3 A1 residue and the other the methylated K4; the limited cleft length confers selectivity for H3K4me2/3, and this recognition is required for recruitment of SAGA to target loci and consequent histone H3 acetylation [PMID:21685874]. Through this reader activity SGF29 maintains H3K4me3 and directs H3K14 acetylation at inducible promoters, coordinating with the SET1/MLL component ASH2L to sustain the H3K4me3 mark itself [PMID:23894581]. As a complex component it interacts with ADA3, GCN5 and SPT3 and is recruited with c-Myc to activate c-Myc target genes, supporting transformation and metastasis [PMID:17334388]. SGF29 supports distinct gene-expression programs across contexts: it sustains pluripotency by interacting with Oct4 and Nanog and maintaining H3K9 acetylation and chromatin accessibility at pluripotency genes in ESCs and pre-implantation embryos [PMID:41843375]; during senescence it forms liquid-like nuclear condensates via Arg207 in its intrinsically disordered region, an activity that together with H3K4me3 binding is required to recruit transcription factors and co-activators and activate senescence genes including CDKN1A [PMID:37935676]; and it is a nononcogenic dependency in acute myeloid leukemia, where its Tudor domain is required for transcription of oncogenes such as MEIS1 and for leukemogenesis [PMID:38048593].","teleology":[{"year":2007,"claim":"Established SGF29 as a physical component of TFTC/STAGA co-activator complexes and linked it to oncogenic transcription, answering whether SGF29 is part of an acetyltransferase complex and has a functional output.","evidence":"Co-IP with ADA3/GCN5/SPT3, ChIP at c-Myc targets, siRNA knockdown with tumor xenograft assays in rat cells","pmids":["17334388"],"confidence":"Medium","gaps":["Did not define the structural basis of SGF29's role in the complex","Direct molecular activity of SGF29 (mark reading) not yet established"]},{"year":2010,"claim":"Determined that the C-terminal tandem Tudor region adopts a discrete, crystallizable fold, setting up high-resolution structural analysis.","evidence":"Preliminary X-ray crystallography of yeast Sgf29 Tudor domain to 1.92 Å","pmids":["20693663"],"confidence":"Medium","gaps":["No ligand-bound structure or functional assay in this report","Binding specificity unknown at this stage"]},{"year":2011,"claim":"Defined the molecular mechanism of SGF29 as an H3K4me2/3 reader via a dual-pocket tandem Tudor cleft and showed this recognition is required for SAGA recruitment and H3 acetylation, answering how SGF29 targets the complex to chromatin.","evidence":"Crystal structures of yeast and human SGF29 Tudor domains bound to H3K4me2/3 peptides, binding-pocket mutagenesis, in vivo ChIP and acetylation assays","pmids":["21685874"],"confidence":"High","gaps":["Does not address SGF29 function outside SAGA recruitment","Cell-type and gene-program specificity not addressed"]},{"year":2013,"claim":"Showed SGF29 belongs to both SAGA and ATAC and coordinates H3K4me3 maintenance with H3K14 acetylation at inducible promoters, extending its reader role to crosstalk with SET1/MLL machinery.","evidence":"siRNA knockdown, ChIP for H3K4me3/H3K14ac and ASH2L, RT-PCR, mass spectrometry complex identification at ER stress genes","pmids":["23894581"],"confidence":"Medium","gaps":["Mechanism by which SGF29 promotes ASH2L association unclear","Direct vs indirect effect on H3K4me3 deposition not resolved"]},{"year":2013,"claim":"Distinguished an acetyltransferase-independent boundary-forming function of Sgf29 in yeast, indicating SGF29 has roles separable from Gcn5 catalytic activity.","evidence":"Yeast genetic boundary assay with domain truncation and in vivo telomere boundary analysis","pmids":["24307402"],"confidence":"Medium","gaps":["Molecular basis of boundary activity unknown","Relevance to human SGF29 not established"]},{"year":2023,"claim":"Revealed that SGF29 forms phase-separated nuclear condensates driven by Arg207 in its IDR, and that condensation acts together with H3K4me3 binding to drive senescence gene transcription, adding a biophysical layer to its co-activator function.","evidence":"R207 mutagenesis, live-cell phase-separation imaging, ChIP-seq, ATAC-seq, RNA-seq and co-activator recruitment in human progenitor cells and fibroblasts","pmids":["37935676"],"confidence":"Medium","gaps":["Whether condensation operates outside senescence is unaddressed","Composition of the condensates not fully defined"]},{"year":2024,"claim":"Identified SGF29's Tudor reader function as a nononcogenic dependency required for AML oncogene transcription and leukemogenesis, nominating it as a therapeutic target.","evidence":"CRISPR-Cas9 domain-focused screen, CRISPR droplet sequencing, in vivo AML models","pmids":["38048593"],"confidence":"Medium","gaps":["Direct Tudor-domain inhibitors not yet validated in this study","Mechanism linking SGF29 specifically to MEIS1 regulation not fully detailed"]},{"year":2024,"claim":"Placed SGF29 functionally in telomere maintenance by promoting the Alternative Lengthening of Telomeres pathway.","evidence":"High-throughput imaging-based CRISPR screen (TAILS) with native FISH readout (preprint)","pmids":["bio_10.1101_2024.11.15.623791"],"confidence":"Low","gaps":["Single screening hit with no SGF29-specific mechanistic follow-up","Not yet peer-reviewed","Connection to its reader/co-activator function unexplored"]},{"year":2026,"claim":"Established a role for SGF29 in maintaining pluripotency through interaction with Oct4 and Nanog and control of H3K9 acetylation and chromatin accessibility, extending its function to developmental gene programs.","evidence":"mESC knockout/knockdown, Co-IP of Sgf29 with Oct4/Nanog, ChIP-seq for H3K9ac and TF binding, ATAC-seq, pre-implantation embryo assays","pmids":["41843375"],"confidence":"Medium","gaps":["Whether Oct4/Nanog binding is direct or complex-mediated not resolved","Structural basis of TF interaction unknown"]},{"year":null,"claim":"It remains unresolved how SGF29's single reader/condensate biochemistry is redirected to produce context-specific gene programs (pluripotency vs senescence vs leukemia) and whether its acetyltransferase-independent and telomere-associated activities reflect a common mechanism.","evidence":"","pmids":[],"confidence":"Low","gaps":["No unifying model for context-specific target selection","ALT/telomere role lacks mechanistic confirmation","Direct Tudor-domain inhibitor pharmacology not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0,3]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[2,5,7]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[5]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[0,3]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,2,3]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,3,5]}],"complexes":["SAGA","ATAC","TFTC/STAGA"],"partners":["ADA3","GCN5","SPT3","ASH2L","MYC","POU5F1","NANOG"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96ES7","full_name":"SAGA-associated factor 29","aliases":["Coiled-coil domain-containing protein 101","SAGA complex-associated factor 29"],"length_aa":293,"mass_kda":33.2,"function":"Chromatin reader component of some histone acetyltransferase (HAT) SAGA-type complexes like the TFTC-HAT, ATAC or STAGA complexes (PubMed:19103755, PubMed:20850016, PubMed:21685874, PubMed:26421618, PubMed:26578293). SGF29 specifically recognizes and binds methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3) (PubMed:20850016, PubMed:21685874, PubMed:26421618, PubMed:26578293). In the SAGA-type complexes, SGF29 is required to recruit complexes to H3K4me (PubMed:20850016). Involved in the response to endoplasmic reticulum (ER) stress by recruiting the SAGA complex to H3K4me, thereby promoting histone H3 acetylation and cell survival (PubMed:23894581). Also binds non-histone proteins that are methylated on Lys residues: specifically recognizes and binds CGAS monomethylated on 'Lys-506' (By similarity)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q96ES7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SGF29","classification":"Not Classified","n_dependent_lines":737,"n_total_lines":1208,"dependency_fraction":0.6100993377483444},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TAF12","stoichiometry":10.0},{"gene":"TRRAP","stoichiometry":10.0},{"gene":"USP22","stoichiometry":4.0},{"gene":"ACTB","stoichiometry":0.2},{"gene":"ENY2","stoichiometry":0.2},{"gene":"SF3B3","stoichiometry":0.2},{"gene":"SF3B5","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SGF29","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoli","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SGF29"},"hgnc":{"alias_symbol":["FLJ32446","TDRD29"],"prev_symbol":["CCDC101"]},"alphafold":{"accession":"Q96ES7","domains":[{"cath_id":"2.30.30.140","chopping":"223-285","consensus_level":"medium","plddt":97.2895,"start":223,"end":285},{"cath_id":"1.10.287","chopping":"1-111","consensus_level":"medium","plddt":89.422,"start":1,"end":111}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96ES7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96ES7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96ES7-F1-predicted_aligned_error_v6.png","plddt_mean":91.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SGF29","jax_strain_url":"https://www.jax.org/strain/search?query=SGF29"},"sequence":{"accession":"Q96ES7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96ES7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96ES7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96ES7"}},"corpus_meta":[{"pmid":"21685874","id":"PMC_21685874","title":"Sgf29 binds histone H3K4me2/3 and is required for SAGA complex recruitment and histone H3 acetylation.","date":"2011","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/21685874","citation_count":211,"is_preprint":false},{"pmid":"23894581","id":"PMC_23894581","title":"A dual role for SAGA-associated factor 29 (SGF29) in ER stress survival by coordination of both histone H3 acetylation and histone H3 lysine-4 trimethylation.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23894581","citation_count":39,"is_preprint":false},{"pmid":"32890768","id":"PMC_32890768","title":"The Ada2/Ada3/Gcn5/Sgf29 histone acetyltransferase module.","date":"2020","source":"Biochimica et biophysica acta. Gene regulatory mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/32890768","citation_count":36,"is_preprint":false},{"pmid":"37935676","id":"PMC_37935676","title":"SGF29 nuclear condensates reinforce cellular aging.","date":"2023","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/37935676","citation_count":31,"is_preprint":false},{"pmid":"17334388","id":"PMC_17334388","title":"Deregulated expression of a novel component of TFTC/STAGA histone acetyltransferase complexes, rat SGF29, in hepatocellular carcinoma: possible implication for the oncogenic potential of c-Myc.","date":"2007","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/17334388","citation_count":29,"is_preprint":false},{"pmid":"38048593","id":"PMC_38048593","title":"Transcriptional control of leukemogenesis by the chromatin reader SGF29.","date":"2024","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/38048593","citation_count":14,"is_preprint":false},{"pmid":"24307402","id":"PMC_24307402","title":"The N-terminus and Tudor domains of Sgf29 are important for its heterochromatin boundary formation function.","date":"2013","source":"Journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24307402","citation_count":12,"is_preprint":false},{"pmid":"26322172","id":"PMC_26322172","title":"SGF29 and Sry pathway in hepatocarcinogenesis.","date":"2015","source":"World journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26322172","citation_count":8,"is_preprint":false},{"pmid":"20693663","id":"PMC_20693663","title":"Cloning, purification, crystallization and preliminary crystallographic analysis of the tandem tudor domain of Sgf29 from Saccharomyces cerevisiae.","date":"2010","source":"Acta crystallographica. Section F, Structural biology and crystallization communications","url":"https://pubmed.ncbi.nlm.nih.gov/20693663","citation_count":5,"is_preprint":false},{"pmid":"41843375","id":"PMC_41843375","title":"Sgf29 regulates pluripotency by maintaining chromatin accessibility and promoting the expression of core transcription factors.","date":"2026","source":"Science China. Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41843375","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.11.15.623791","title":"Identification of Novel Modulators of the ALT Pathway Through a Native FISH-Based Optical Screen","date":"2024-11-15","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.15.623791","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6820,"output_tokens":2554,"usd":0.029385,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9711,"output_tokens":3476,"usd":0.067727,"stage2_stop_reason":"end_turn"},"total_usd":0.097112,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"Crystal structures of the tandem Tudor domains of S. cerevisiae and human SGF29 bound to H3K4me2 and H3K4me3 peptides revealed that the two Tudor domains pack face-to-face, with one pocket accommodating the H3A1 residue and the other the methylated K4 residue. The limited cleft length between the two pockets confers selectivity for H3K4me2/3. In vitro and in vivo functional assays demonstrated that H3K4me2/3 recognition by SGF29 is required for SAGA complex recruitment to target gene loci and consequent histone H3 acetylation.\",\n      \"method\": \"Crystal structure (X-ray crystallography), peptide binding assays, in vivo ChIP and histone acetylation assays, mutagenesis of binding pockets\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structures at ~2 Å with mutagenesis and orthogonal in vitro/in vivo functional validation in a single rigorous study\",\n      \"pmids\": [\"21685874\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The tandem Tudor domain at the C-terminus of S. cerevisiae Sgf29 was successfully crystallized and diffracted to 1.92 Å resolution, confirming the domain adopts a distinct structural fold amenable to high-resolution analysis.\",\n      \"method\": \"X-ray crystallography (preliminary crystallographic analysis)\",\n      \"journal\": \"Acta crystallographica. Section F, Structural biology and crystallization communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — structural data from a single crystallographic report with no functional follow-up in this paper\",\n      \"pmids\": [\"20693663\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Rat SGF29 directly interacted with rADA3 (direct interaction) and co-immunoprecipitated with rGCN5 and rSPT3, establishing it as a component of the TFTC/STAGA complexes. SGF29 was recruited to c-Myc target gene promoters together with c-Myc and activated c-Myc target gene expression. Knockdown of rSGF29 suppressed c-Myc target gene expression and inhibited anchorage-independent growth, tumorigenicity, and lung metastasis.\",\n      \"method\": \"Co-immunoprecipitation, ChIP, gene expression assays, siRNA knockdown, in vivo tumor xenograft assay\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP with multiple subunits, ChIP, and functional KD phenotype; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"17334388\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Human SGF29 is a subunit of both the SAGA and ATAC histone acetyltransferase/co-activator complexes. SGF29 knockdown impaired transcription of ER stress genes GRP78 and CHOP, and reduced H3K14 acetylation at these loci. Additionally, SGF29 was required for maintenance of H3K4me3 at these promoters prior to ER stress; reduced H3K4me3 in SGF29-depleted cells correlated with decreased association of ASH2L (a core SET1/MLL complex component) at these gene loci, indicating a role for SGF29 in coordinating both H3K4me3 maintenance and H3K14 acetylation.\",\n      \"method\": \"siRNA knockdown, ChIP, quantitative RT-PCR, mass spectrometry-based complex identification\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD with multiple chromatin readouts (ChIP for H3K4me3, H3K14ac, and ASH2L binding) in a single lab\",\n      \"pmids\": [\"23894581\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In S. cerevisiae, domain analysis identified two minimal boundary-forming regions in Sgf29: the N-terminal region (aa 1–12) and the Tudor domain-containing C-terminal region (aa 110–255). Critically, the boundary formation activity of these minimal regions was shown to be independent of Gcn5 acetyltransferase activity, and in vivo analysis showed Sgf29 and Gcn5 perform distinct functions at native telomere boundary regions.\",\n      \"method\": \"Yeast genetic boundary assay, domain deletion/truncation analysis, in vivo telomere boundary assay\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain truncation with epistasis analysis (Gcn5-independent boundary function), single lab\",\n      \"pmids\": [\"24307402\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SGF29 forms liquid-like nuclear condensates during cellular senescence in human mesenchymal progenitor cells and fibroblasts via phase separation. Arg207 within the intrinsically disordered region is the key residue for condensate formation. Both condensate formation and H3K4me3 binding are required for SGF29 to establish its chromatin localization, recruit transcription factors and co-activators to specific genomic loci, and activate senescence-associated genes including CDKN1A. Condensate formation alone is not sufficient for H3K4me3 binding or transactivation.\",\n      \"method\": \"Mutagenesis (R207 mutation), live-cell imaging of phase separation, ChIP-seq, ATAC-seq, RNA-seq, co-activator recruitment assays\",\n      \"journal\": \"Cell discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis of key IDR residue with orthogonal epigenomic and transcriptomic validation; single lab\",\n      \"pmids\": [\"37935676\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CRISPR-Cas9 domain-focused screen identified SGF29 as required for transcription of AML oncogenes including MEIS1. SGF29 deletion impaired leukemogenesis across multiple AML subtype models, establishing the SGF29 Tudor domain (H3K4me3 reader function) as a nononcogenic dependency in AML.\",\n      \"method\": \"CRISPR-Cas9 domain-focused library screen, CRISPR droplet sequencing, in vivo leukemia models\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic CRISPR screen with in vivo functional validation in multiple AML models; single lab\",\n      \"pmids\": [\"38048593\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In mouse ESCs, Sgf29 knockout reduced H3K9ac and chromatin accessibility at promoters and enhancers of pluripotency genes, triggering differentiation. Sgf29 was shown to interact with Oct4 and Nanog (but not Sox2) to co-regulate pluripotency gene expression. Sgf29 KO reduced Oct4 binding to Nanog and Klf4 loci. Sgf29 knockdown in pre-implantation embryos reduced blastocyst rate and decreased H3K9ac, with aberrant Oct4 and Nanog expression.\",\n      \"method\": \"Knockout/knockdown in mESCs, co-immunoprecipitation (Sgf29 with Oct4/Nanog), ChIP-seq for H3K9ac and transcription factor binding, ATAC-seq, pre-implantation embryo assays\",\n      \"journal\": \"Science China. Life sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO + Co-IP + ChIP-seq + ATAC-seq with multiple orthogonal readouts; single lab\",\n      \"pmids\": [\"41843375\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A high-throughput imaging-based CRISPR screen (TAILS) identified SGF29 as a promoter of the Alternative Lengthening of Telomeres (ALT) pathway, placing SGF29 functionally in telomere maintenance via recombination.\",\n      \"method\": \"High-throughput CRISPR screen with native FISH-based optical readout (TAILS)\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single screening hit from a preprint, no mechanistic follow-up on SGF29 specifically in this paper\",\n      \"pmids\": [\"bio_10.1101_2024.11.15.623791\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"SGF29 is a subunit of the SAGA (and related ATAC) transcriptional co-activator complex that uses its tandem Tudor domains to selectively bind H3K4me2/3 histone marks—through a structurally defined dual-pocket mechanism—thereby recruiting the SAGA complex to active promoters and promoting GCN5-mediated histone H3 acetylation; it additionally forms phase-separated nuclear condensates (via Arg207 in its IDR) during senescence to reinforce transcription of senescence genes, interacts with Oct4 and Nanog to maintain pluripotency chromatin accessibility, and is required for expression of AML oncogenes and leukemogenesis, making its Tudor domain an emerging therapeutic target.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SGF29 is a histone-mark reader subunit of the SAGA and ATAC histone acetyltransferase/co-activator complexes that couples recognition of active-promoter chromatin to GCN5-family histone acetylation [#0, #3]. Its tandem Tudor domains pack face-to-face to form a dual-pocket cleft in which one pocket binds the H3 A1 residue and the other the methylated K4; the limited cleft length confers selectivity for H3K4me2/3, and this recognition is required for recruitment of SAGA to target loci and consequent histone H3 acetylation [#0]. Through this reader activity SGF29 maintains H3K4me3 and directs H3K14 acetylation at inducible promoters, coordinating with the SET1/MLL component ASH2L to sustain the H3K4me3 mark itself [#3]. As a complex component it interacts with ADA3, GCN5 and SPT3 and is recruited with c-Myc to activate c-Myc target genes, supporting transformation and metastasis [#2]. SGF29 supports distinct gene-expression programs across contexts: it sustains pluripotency by interacting with Oct4 and Nanog and maintaining H3K9 acetylation and chromatin accessibility at pluripotency genes in ESCs and pre-implantation embryos [#7]; during senescence it forms liquid-like nuclear condensates via Arg207 in its intrinsically disordered region, an activity that together with H3K4me3 binding is required to recruit transcription factors and co-activators and activate senescence genes including CDKN1A [#5]; and it is a nononcogenic dependency in acute myeloid leukemia, where its Tudor domain is required for transcription of oncogenes such as MEIS1 and for leukemogenesis [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established SGF29 as a physical component of TFTC/STAGA co-activator complexes and linked it to oncogenic transcription, answering whether SGF29 is part of an acetyltransferase complex and has a functional output.\",\n      \"evidence\": \"Co-IP with ADA3/GCN5/SPT3, ChIP at c-Myc targets, siRNA knockdown with tumor xenograft assays in rat cells\",\n      \"pmids\": [\"17334388\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Did not define the structural basis of SGF29's role in the complex\", \"Direct molecular activity of SGF29 (mark reading) not yet established\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Determined that the C-terminal tandem Tudor region adopts a discrete, crystallizable fold, setting up high-resolution structural analysis.\",\n      \"evidence\": \"Preliminary X-ray crystallography of yeast Sgf29 Tudor domain to 1.92 Å\",\n      \"pmids\": [\"20693663\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No ligand-bound structure or functional assay in this report\", \"Binding specificity unknown at this stage\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined the molecular mechanism of SGF29 as an H3K4me2/3 reader via a dual-pocket tandem Tudor cleft and showed this recognition is required for SAGA recruitment and H3 acetylation, answering how SGF29 targets the complex to chromatin.\",\n      \"evidence\": \"Crystal structures of yeast and human SGF29 Tudor domains bound to H3K4me2/3 peptides, binding-pocket mutagenesis, in vivo ChIP and acetylation assays\",\n      \"pmids\": [\"21685874\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Does not address SGF29 function outside SAGA recruitment\", \"Cell-type and gene-program specificity not addressed\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showed SGF29 belongs to both SAGA and ATAC and coordinates H3K4me3 maintenance with H3K14 acetylation at inducible promoters, extending its reader role to crosstalk with SET1/MLL machinery.\",\n      \"evidence\": \"siRNA knockdown, ChIP for H3K4me3/H3K14ac and ASH2L, RT-PCR, mass spectrometry complex identification at ER stress genes\",\n      \"pmids\": [\"23894581\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mechanism by which SGF29 promotes ASH2L association unclear\", \"Direct vs indirect effect on H3K4me3 deposition not resolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Distinguished an acetyltransferase-independent boundary-forming function of Sgf29 in yeast, indicating SGF29 has roles separable from Gcn5 catalytic activity.\",\n      \"evidence\": \"Yeast genetic boundary assay with domain truncation and in vivo telomere boundary analysis\",\n      \"pmids\": [\"24307402\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Molecular basis of boundary activity unknown\", \"Relevance to human SGF29 not established\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealed that SGF29 forms phase-separated nuclear condensates driven by Arg207 in its IDR, and that condensation acts together with H3K4me3 binding to drive senescence gene transcription, adding a biophysical layer to its co-activator function.\",\n      \"evidence\": \"R207 mutagenesis, live-cell phase-separation imaging, ChIP-seq, ATAC-seq, RNA-seq and co-activator recruitment in human progenitor cells and fibroblasts\",\n      \"pmids\": [\"37935676\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Whether condensation operates outside senescence is unaddressed\", \"Composition of the condensates not fully defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified SGF29's Tudor reader function as a nononcogenic dependency required for AML oncogene transcription and leukemogenesis, nominating it as a therapeutic target.\",\n      \"evidence\": \"CRISPR-Cas9 domain-focused screen, CRISPR droplet sequencing, in vivo AML models\",\n      \"pmids\": [\"38048593\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct Tudor-domain inhibitors not yet validated in this study\", \"Mechanism linking SGF29 specifically to MEIS1 regulation not fully detailed\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Placed SGF29 functionally in telomere maintenance by promoting the Alternative Lengthening of Telomeres pathway.\",\n      \"evidence\": \"High-throughput imaging-based CRISPR screen (TAILS) with native FISH readout (preprint)\",\n      \"pmids\": [\"bio_10.1101_2024.11.15.623791\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single screening hit with no SGF29-specific mechanistic follow-up\", \"Not yet peer-reviewed\", \"Connection to its reader/co-activator function unexplored\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Established a role for SGF29 in maintaining pluripotency through interaction with Oct4 and Nanog and control of H3K9 acetylation and chromatin accessibility, extending its function to developmental gene programs.\",\n      \"evidence\": \"mESC knockout/knockdown, Co-IP of Sgf29 with Oct4/Nanog, ChIP-seq for H3K9ac and TF binding, ATAC-seq, pre-implantation embryo assays\",\n      \"pmids\": [\"41843375\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Whether Oct4/Nanog binding is direct or complex-mediated not resolved\", \"Structural basis of TF interaction unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how SGF29's single reader/condensate biochemistry is redirected to produce context-specific gene programs (pluripotency vs senescence vs leukemia) and whether its acetyltransferase-independent and telomere-associated activities reflect a common mechanism.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No unifying model for context-specific target selection\", \"ALT/telomere role lacks mechanistic confirmation\", \"Direct Tudor-domain inhibitor pharmacology not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [2, 5, 7]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 3, 5]}\n    ],\n    \"complexes\": [\"SAGA\", \"ATAC\", \"TFTC/STAGA\"],\n    \"partners\": [\"ADA3\", \"GCN5\", \"SPT3\", \"ASH2L\", \"MYC\", \"POU5F1\", \"NANOG\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":5,"faith_pct":80.0}}