Affinage

SMARCB1

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 · UniProt Q12824

Length
385 aa
Mass
44.1 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMARCB1 (BAF47/INI1/SNF5) is an essential core subunit of the SWI/SNF (BAF/PBAF) ATP-dependent chromatin-remodeling complexes that functions as a tumor suppressor by stabilizing complex occupancy on chromatin and shaping enhancer and promoter activity genome-wide (PMID:7579694, PMID:28945250). It does not govern complex assembly but is required for stable BAF complex residence on chromatin; its re-expression in deficient cells increases genome-wide BAF occupancy, drives widespread enhancer activation, and opposes Polycomb-mediated repression at bivalent promoters (PMID:28945250, PMID:31033435). Within the complex, SMARCB1 multimerizes through its Rpt1 and Rpt2 motifs and docks onto BAF155 via a defined Rpt1–SWIRM interface resolved by crystallography (PMID:19398554, PMID:28438634). SMARCB1 loss is the initiating lesion in rhabdoid tumors and related cancers; mechanistically, loss collapses normal regulation by enabling DCAF5-mediated proteasomal degradation of residual SMARCB1-deficient SWI/SNF complexes, such that DCAF5 removal restores complex accumulation, chromatin rebinding, and reversal of the cancer state (PMID:38538798). Through these chromatin functions, SMARCB1 enforces growth arrest: it represses cyclin D1 in an HDAC-dependent manner, induces p16ink4a to activate the RB pathway and drive G0/G1 arrest, and represses mitotic genes including PLK1 while activating interferon-stimulated and senescence programs (PMID:12138206, PMID:12149641, PMID:17699849). SMARCB1 also acts as a direct promoter-bound repressor of IL6 and antagonizes IL6/JAK/STAT3 signaling, suppresses RhoA activity to organize the actin cytoskeleton, and in renal medullary carcinoma reverses a MYC/ferroptosis-resistance transcriptional program (PMID:15150092, PMID:38355560, PMID:32492816, PMID:37236926). Whether SMARCB1 loss produces rhabdoid tumors or schwannomas is dictated by the developmental stage and cell lineage in which inactivation occurs (PMID:28824165). Independently of its chromatin role, SMARCB1/INI1 is incorporated into HIV-1 virions and binds HIV-1 integrase through an Rpt1-containing integrase-binding domain that structurally mimics TAR RNA, constraining integrase conformation and modulating viral late events (PMID:16945155, PMID:23593299, PMID:33980829).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Established that SMARCB1's ortholog is a physical, integral component of a SWI/SNF-class chromatin-remodeling complex rather than a free-standing factor, defining its molecular context.

    Evidence Co-immunoprecipitation and biochemical fractionation of Drosophila SNR1 with BRM, plus genetic interaction with trithorax

    PMID:7579694

    Open questions at the time
    • Did not define which human SWI/SNF subunits SMARCB1 contacts directly
    • Mechanism of recruitment to target loci unresolved
  2. 1998 High

    Identified a recruitment logic by showing the SET domain of ALL-1/Trithorax binds INI1/SNF5, linking SWI/SNF to homeotic/leukemia-relevant target loci.

    Evidence Yeast two-hybrid, in vitro pulldown, Co-IP, and polytene chromosome co-localization across human and Drosophila

    PMID:9539705

    Open questions at the time
    • Functional consequence of the interaction at endogenous human loci untested
    • Did not address remodeling vs targeting roles
  3. 2002 High

    Defined SMARCB1 as a growth suppressor acting through the RB pathway, resolving how its loss promotes proliferation in rhabdoid tumors.

    Evidence Re-expression of INI1/hSNF5 in deficient cells with ChIP at cyclin D1, HDAC dependence, p16ink4a induction, RB hypophosphorylation, and epistatic rescue with cyclin D1, SV40 T/t, or HPV E7

    PMID:12082626 PMID:12138206 PMID:12149641

    Open questions at the time
    • How chromatin remodeling activity connects mechanistically to cyclin D1/p16 regulation not fully resolved
    • Rpt1/Rpt2 requirement for growth suppression mapped but not structurally explained
  4. 2003 High

    Showed SMARCB1's ortholog is a tissue-selective, locus-directing subunit and mapped Repeat 2 as critical for protein interaction and growth control.

    Evidence Drosophila temperature-sensitive snr1E1 allele, Co-IP, in vitro binding, and genome-wide polytene localization showing partial BRM co-occupancy

    PMID:12482982 PMID:12645932

    Open questions at the time
    • Tissue-selectivity mechanism in mammals untested
    • Did not define how Repeat 2 contacts the SET domain structurally
  5. 2004 High

    Linked SMARCB1 to cytoskeletal regulation, expanding its role beyond cell-cycle control.

    Evidence Tetracycline-inducible INI1 re-expression with genome-wide microarray, ER-fusion direct-target mapping, and RhoA activity assay

    PMID:15150092 PMID:15454538

    Open questions at the time
    • Direct molecular link between SMARCB1 and RhoA pathway not established
    • Whether Rho regulation is chromatin-dependent unknown
  6. 2006 Medium

    Revealed a non-chromatin function: INI1 is packaged into HIV-1 virions and is required for productive particle production and infectivity.

    Evidence HIV-1 infection of INI1-null rhabdoid lines with re-expression rescue and reverse transcriptase assays; identification of SNR1 Thr102 phosphorylation by DYRK2/MNB

    PMID:16671894 PMID:16945155

    Open questions at the time
    • Single-lab virology findings without independent replication
    • Functional role of Thr102 phosphorylation in mammals untested
  7. 2007 High

    Identified PLK1 repression and interferon/senescence activation as functionally relevant downstream programs of SMARCB1 controlling mitotic fidelity.

    Evidence cDNA microarray, qRT-PCR, primary tumor IHC, and RNAi knockdown of PLK1 showing mitotic arrest and apoptosis in INI1-deficient cells

    PMID:17699849

    Open questions at the time
    • Direct promoter occupancy at PLK1 vs indirect effect not fully distinguished
    • Interferon gene activation mechanism unresolved
  8. 2009 High

    Defined the Rpt1/Rpt2 multimerization domain and connected multimerization to nuclear retention and HIV-1 integrase co-localization.

    Evidence Protein purification, reverse yeast two-hybrid, deletion analysis, Co-IP, in vitro strand transfer, and nuclear localization imaging

    PMID:19398554

    Open questions at the time
    • In vivo relevance of multimerization to SWI/SNF function not addressed
    • DNA minor-groove binding role left preliminary
  9. 2013 High

    Demonstrated in vivo tumor-suppressor activity through Igfbp7/PI3K-AKT regulation and across multiple cancer types, extending SMARCB1 loss to causal pathogenesis.

    Evidence Retroviral re-expression with xenograft rescue, Igfbp7 re-expression, AKT inhibition in mouse tumor cells, and re-expression phenotyping in epithelioid sarcoma; HIV-1 integrase/LEDGF/DNA complex cryo-EM and stoichiometry

    PMID:23576573 PMID:23593299 PMID:23851500

    Open questions at the time
    • How SMARCB1 selects Igfbp7 vs other targets unresolved
    • Whether Igfbp7/AKT axis operates in human rhabdoid tumors untested
  10. 2014 High

    Established the central chromatin mechanism: SMARCB1 stabilizes BAF complex occupancy genome-wide, activating enhancers and opposing Polycomb, without affecting complex assembly.

    Evidence ChIP-seq for BAF occupancy with SMARCB1 re-expression distinguishing BAF and PBAF enhancer/promoter roles; Co-IP placing BAF47 in SWI/SNF and N-CoR-1 complexes during myogenesis

    PMID:25271443 PMID:28945250

    Open questions at the time
    • Molecular basis for chromatin stabilization vs assembly distinction not structurally defined
    • How the same subunit partitions between activating and repressive complexes unresolved
  11. 2017 High

    Provided structural basis for SMARCB1's interaction with the complex and dissected lineage-specific tumor outcomes.

    Evidence Crystal structure of BAF155 SWIRM–BAF47 RPT1 with ITC and NMR validation; stage- and lineage-specific conditional knockout mice generating rhabdoid tumors vs schwannomas

    PMID:28438634 PMID:28824165

    Open questions at the time
    • Structure of the full SMARCB1 within the assembled complex not resolved
    • Molecular determinants linking developmental stage to tumor type unknown
  12. 2019 High

    Defined SMARCB1's role in development as a repressor of bivalent genes and super-enhancers required specifically for neural induction.

    Evidence SMARCB1 loss-of-function in hESCs and iPSCs with ChIP-seq, ATAC-seq, directed differentiation, and cerebral organoids showing differentiation-state-dependent effects

    PMID:31033435 PMID:32912900

    Open questions at the time
    • Mechanism of cell-type-selective requirement unresolved
    • How super-enhancer silencing is enforced by SMARCB1 not defined
  13. 2020 High

    Identified IL6/JAK/STAT3 as a SMARCB1-deficiency vulnerability and SMARCB1 as a direct IL6 promoter repressor, linking chromatin accessibility changes to a druggable signaling axis.

    Evidence ATAC-seq, ChIP at IL6 promoter, loss/gain-of-function, orthotopic xenografts and PDX with STAT3 inhibitor TTI-101; NUP210 enhancer ChIP-seq in liver cancer

    PMID:32492816 PMID:33239431 PMID:38355560

    Open questions at the time
    • Whether STAT3 activation is uniform across SMARCB1-deficient tumor types untested
    • Context-dependent up- vs down-regulation by SMARCB1 not mechanistically unified
  14. 2021 High

    Solved how SMARCB1 modulates HIV-1 integrase by showing the Rpt1 domain structurally mimics TAR RNA and competes for integrase binding.

    Evidence NMR structure of INI1 Rpt1, mutational analysis, competition binding (IC50), and computational modeling of the IN-CTD interface

    PMID:33980829

    Open questions at the time
    • Physiological relevance during natural infection not established
    • Link between integrase-binding and SWI/SNF chromatin function unexplored
  15. 2023 High

    Showed SMARCB1 reshapes 3D enhancer architecture and reverses oncogenic transcriptional switches, including MYC enhancer looping and a MYC/ferroptosis-resistance program in renal medullary carcinoma.

    Evidence Patient-derived organoid multi-omics, chromosome conformation capture, single-cell RNA/ATAC-seq, SMARCB1 re-expression, ferroptosis assays, and hypoxia-induced SMARCB1 degradation in renal cells and a sickle cell trait mouse model

    PMID:37186844 PMID:37236926 PMID:38040699

    Open questions at the time
    • Patient-specific enhancer heterogeneity mechanism unresolved
    • Pathway linking hypoxia to SMARCB1 degradation not fully defined
  16. 2024 High

    Reframed SMARCB1-mutant cancer as a consequence of DCAF5-mediated degradation of residual SWI/SNF complexes, and identified CBP/p300-driven KREMEN2 as a selective vulnerability.

    Evidence Genome-wide CRISPR screen, DCAF5 depletion, ChIP-seq, and in vivo xenografts; synthetic-lethal screen with H3K27ac/CBP/p300 ChIP-seq and CBP/p300 inhibition at the KREMEN2 locus

    PMID:38538798 PMID:38839769

    Open questions at the time
    • How DCAF5 recognizes incompletely assembled complexes structurally undefined
    • Generalizability of KREMEN2 vulnerability across SMARCB1-deficient tumors untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SMARCB1 mechanistically couples its structural role in BAF complex stabilization to the diverse target-gene programs (cyclin D1, p16, PLK1, IL6, MYC) and how this is read out in a cell-type- and developmental-stage-specific manner remains unresolved.
  • No unified structural model of SMARCB1 within the assembled complex on chromatin
  • Determinants of lineage-specific target selection unknown
  • Reconciliation of SMARCB1 as both activator and repressor at different loci incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0005198 structural molecule activity 2 GO:0042393 histone binding 2 GO:0003677 DNA binding 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
BRM/BRG1DCAF5HIV-1 INTEGRASELEDGF/P75MYODNUP210SMARCC1
Complex memberships
N-CoR-1 repressor complexPBAFSWI/SNF (BAF)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Drosophila SNR1 (ortholog of human SMARCB1/INI1) physically associates with the Brahma (BRM) protein and is a component of a large (>2×10^6 Da) SWI/SNF-like chromatin-remodeling complex in Drosophila, as demonstrated by co-immunoprecipitation from fly extracts. SNR1 and BRM genetically interact with trithorax (trx), supporting a cooperative role in maintaining homeotic gene transcription. Co-immunoprecipitation from Drosophila extracts; genetic interaction analysis; biochemical fractionation Molecular biology of the cell High 7579694
1998 The C-terminal SET domain of ALL-1 (human) and TRITHORAX (Drosophila) physically interact with INI1/hSNF5 (human) and SNR1 (Drosophila), respectively. Interaction was demonstrated by yeast two-hybrid, in vitro binding assays, and co-immunoprecipitation from cultured cells and transgenic flies. SNR1 co-localizes with ~half of TRX binding sites on polytene chromosomes, suggesting SWI/SNF recruitment to ALL-1/TRX target loci via these physical contacts. Yeast two-hybrid screen; in vitro pulldown; co-immunoprecipitation from cells and transgenic flies; polytene chromosome immunostaining Proceedings of the National Academy of Sciences of the United States of America High 9539705
2002 Re-expression of INI1/hSNF5 in INI1-deficient rhabdoid tumor cells (MON) causes G0/G1 cell cycle arrest and flat cell formation. INI1 directly represses cyclin D1 transcription in an HDAC-dependent manner: chromatin immunoprecipitation showed INI1 is recruited to the cyclin D1 promoter, correlating with HDAC1 recruitment and histone deacetylation at that promoter. Ectopic cyclin D1 expression from a heterologous promoter rescued the INI1-mediated arrest. Retroviral re-expression; flow cytometry; ChIP; HDAC inhibitor experiments; rescue with ectopic cyclin D1; truncation analysis Molecular and cellular biology High 12138206
2002 Re-expression of hSNF5/INI1/BAF47 in INI1-deficient rhabdoid tumor cell lines induces G1 arrest associated with strong induction of p16ink4a and hypophosphorylation (activation) of RB, establishing that hSNF5 signals upstream of RB to induce growth arrest. Co-expression of SV40 T/t antigen or HPV-16 E7 (which inactivates RB) abrogated hSNF5-induced arrest. Retroviral re-expression; flow cytometry; Western blot; rescue with SV40 T/t or HPV E7 Oncogene High 12149641
2002 Re-introduction of INI1 into INI1-deficient cells causes G1 arrest and apoptosis (detected by cleaved PARP). Deletion analysis identified Repeats 1 and 2 of INI1 as required for growth suppression in a colony formation assay. Recombinant adenovirus-mediated overexpression; flow cytometry; BrdU incorporation; colony formation; PARP cleavage assay; deletion mutagenesis Oncogene High 12082626
2003 Drosophila SNR1 is an essential but tissue-selective subunit of the Brm (SWI/SNF) complex. A temperature-sensitive allele (snr1E1) with a single amino acid substitution in the conserved Repeat 2 region reduces Brm complex function. SNR1 can make direct contacts through its Repeat 2 region with the SET domain of Trithorax (TRX), and snr1E1 is partially defective for TRX association, establishing Repeat 2 as critical for protein–protein interaction and growth control. Genetic allele analysis; temperature-shift experiments; Co-IP; in vitro binding; polytene chromosome immunostaining Molecular and cellular biology High 12482982
2003 Drosophila SNR1 is required for a subset of Brm complex functions in vivo; SNR1-deficient imaginal tissues show altered gene expression patterns. Genome-wide localization shows SNR1 and BRM co-occupy many chromosomal loci but SNR1 is not required in all tissues dependent on BRM, indicating SNR1 acts as an optional subunit directing complex activity to specific loci. Genetic loss-of-function analysis; polytene chromosome immunostaining; in vivo somatic clone analysis Developmental biology Medium 12645932
2004 Re-induction of hSNF5/INI1 in rhabdoid tumor cells leads to reversible G1 arrest, down-regulation of DNA replication complex components, and dramatic reorganization of the actin cytoskeleton including disruption of actin stress fibers and focal adhesions. INI1 induction strongly decreases RhoA GTPase activity, suggesting that INI1 regulates actin organization through the Rho pathway. Tetracycline-inducible expression system; genome-wide microarray (22,000 genes); estrogen receptor fusion to identify direct targets; Rho activity assay; cell morphology imaging Cancer research High 15150092
2004 In Drosophila, SNR1 mediates associations between the Brm chromatin-remodeling complex and CyclinE/CDK2 both in vitro and in vivo. Disruption of snr1 suppresses DmcycE phenotypes and loss of snr1 function reduces transcription of the G2-M regulator string/cdc25, implicating SNR1 in G1-S control and G2-M progression. In vitro binding assay; genetic epistasis (double mutant analysis); transcription assay Genetics Medium 15454538
2006 Drosophila DYRK2 (dDYRK2) and Minibrain (MNB) interact with SNR1 (the SMARCB1 ortholog) as demonstrated by yeast two-hybrid and co-immunoprecipitation. Both kinases phosphorylate SNR1 at Thr102 in vitro and in vivo, representing the first identified phosphorylation of SNR1 or its homologs. Yeast two-hybrid; co-immunoprecipitation; in vitro kinase assay; in vivo phosphorylation The Biochemical journal Medium 16671894
2006 INI1 is specifically incorporated into HIV-1 virions. In INI1-deficient cells, HIV-1 particle production is severely reduced and infectivity is impaired; re-introduction of INI1 rescues particle production. Virions produced from INI1-null cells are defective for early and late reverse transcription products and for exogenous reverse transcriptase activity. HIV-1 infection of INI1-deficient rhabdoid cell lines; retroviral re-expression; RT assay; transduction assay Retrovirology Medium 16945155
2007 Re-introduction of INI1 into rhabdoid cells activates interferon-stimulated genes at early time points, senescence markers at late time points, and represses mitotic genes including PLK1. RNAi knockdown of PLK1 in INI1-deficient rhabdoid cells causes mitotic arrest, aberrant nuclear division, and apoptosis, establishing PLK1 as a functionally relevant downstream effector of INI1. cDNA microarray; qRT-PCR; Western blot; IHC of primary tumors; RNAi knockdown; cell cycle/apoptosis assays; IFN treatment Clinical cancer research High 17699849
2009 INI1/hSNF5 forms multimeric structures; the Rpt1 and Rpt2 motifs constitute the minimal multimerization domain. Multimerization-defective mutants (identified by reverse yeast two-hybrid) are defective for nuclear retention, co-localization with HIV-1 integrase, and the transdominant inhibitory effect of the S6 fragment on HIV-1. INI1 also binds DNA in the minor groove; acceptor DNA binding may be required for stimulation of in vitro strand transfer by integrase. Protein purification; reverse yeast two-hybrid; deletion analysis; co-immunoprecipitation; in vitro strand transfer assay; nuclear localization imaging The Journal of biological chemistry High 19398554
2012 The SNR1/SNF5 subunit of the Drosophila Brm (SWI/SNF) complex controls RNA polymerase II elongation and pre-mRNA splicing at ecdysone-responsive genes. RNAi knockdown or conditional loss-of-function alleles show that a loss-of-function SNR1 subunit alters chromatin accessibility, RNA Pol II elongation, and splicing of specific hormone-regulated genes, restricting BRM-dependent nucleosome remodeling downstream of the promoter. RNAi knockdown in cultured Drosophila cells and transgenic flies; conditional mutant alleles; transcriptome profiling; chromatin accessibility assays Nucleic acids research Medium 22467207
2013 Restoration of Smarcb1 in Smarcb1-deficient mouse tumor cells abolishes xenograft growth and restores sensitivity to apoptosis without inducing growth arrest in vitro. Smarcb1 is required for transcriptional activation of Igfbp7 (a tumor suppressor); Smarcb1-deficient cells show persistent PI3K-mediated AKT activation, and AKT inhibition reduces proliferation and xenograft growth. Re-introduction of Igfbp7 alone inhibits tumor development. Retroviral re-expression; xenograft assay; AKT inhibitor treatment; gene expression profiling; Igfbp7 rescue experiment Oncogene High 23851500
2013 Restoration of SMARCB1 expression in epithelioid sarcoma cell line VAESBJ (which has a homozygous SMARCB1 deletion) significantly reduces cell proliferation, anchorage-independent growth, and cell migration, establishing a direct causal role for SMARCB1 loss in epithelioid sarcoma pathogenesis. SMARCB1 re-expression; colony formation; soft agar assay; wound-healing/migration assay Molecular cancer therapeutics Medium 23576573
2013 The INI1-Rpt1 integrase-binding domain (IBD) forms a stable complex with HIV-1 integrase (IN), LEDGF/p75, and viral U5 DNA at a stoichiometry of 4 IN:2 LEDGF:2 INI1-IBD:2 DNA determined by mass spectrometry and fluorescence correlation spectroscopy. INI1-IBD inhibits the 3' processing reaction but not specific viral DNA binding. Cryo-EM locates INI1-IBD within the cellular DNA-binding site of the IN/LEDGF complex, constraining IN in a stable conformation that prevents non-specific interactions. In vitro reconstitution of multiprotein complex; mass spectrometry stoichiometry; fluorescence correlation spectroscopy; in vitro integration/3'-processing assay; cryo-electron microscopy PloS one High 23593299
2014 BAF47 (SMARCB1) loss destabilizes BAF complexes on chromatin without significantly altering complex assembly or integrity. Rescue of BAF47 in BAF47-deficient sarcoma cell lines increases genome-wide BAF complex occupancy (measured by ChIP-seq), leading to widespread enhancer activation and opposition of Polycomb-mediated repression at bivalent promoters. Two distinct mSWI/SNF assemblies (BAF and PBAF) differentially regulate enhancers and promoters, respectively. ChIP-seq for BAF complex occupancy; genome-wide enhancer and promoter analysis; re-expression of SMARCB1 in deficient cell lines Nature genetics High 28945250
2014 BAF47/INI1 interacts with MyoD and is part of both the SWI/SNF remodeling complex and the N-CoR-1 repressor complex in proliferating myoblasts. Upon myogenic differentiation, BAF47 shifts toward the N-CoR-1 complex. BAF47 downregulation disrupts both the proliferation and differentiation gene programs, and only BAF47 (not BRG1) is essential for irreversible cell cycle exit during myoblast terminal differentiation. Co-immunoprecipitation; siRNA knockdown; ChIP; gene expression analysis during differentiation PloS one Medium 25271443
2016 In Drosophila imaginal epithelial tissues, Snr1 (SMARCB1 ortholog) prevents neoplastic overgrowth by maintaining normal endosomal trafficking-mediated signaling. Unlike loss of any other SWI/SNF subunit, snr1 depletion alone induces neoplastic tumorigenic overgrowth. Snr1 is found in both nucleus and cytoplasm, and its loss aberrantly activates Notch, JNK, and JAK/STAT signaling pathways. Genetic loss-of-function (tissue-specific RNAi/clones); immunofluorescence localization; pathway reporter assays Cancer research Medium 27923836
2017 Crystal structure of the BAF155 SWIRM domain in complex with the BAF47 (SMARCB1) Repeat 1 (RPT1) domain was determined at high resolution. Extensive mutagenesis combined with isothermal titration calorimetry and NMR titrations confirmed the interface residues. The SWIRM domain of BAF155 is a modular domain responsible for interaction with BAF47, functionally distinct from DNA-binding SWIRM domains. X-ray crystallography; mutagenesis; isothermal titration calorimetry (ITC); NMR titration Journal of molecular biology High 28438634
2017 Timing of Smarcb1 and Nf2 inactivation determines tumor type: early Smarcb1 loss in neural crest initiates rhabdoid tumors in cranial nerves and meninges, whereas Smarcb1 loss at a later stage in the Schwann cell lineage combined with biallelic Nf2 inactivation generates schwannomas. This establishes a developmental stage-specific and cell-type-specific mechanism governing the two distinct SMARCB1-associated tumor syndromes. Tissue- and developmental stage-specific conditional knockout mice; histological and molecular profiling of resulting tumors Nature communications High 28824165
2019 In human embryonic stem cells (hESCs), SMARCB1 represses bivalent genes and antagonizes chromatin accessibility at super-enhancers. SMARCB1 is specifically required for neural induction but dispensable for mesodermal or endodermal differentiation, and is essential for super-enhancer silencing during neural differentiation conditions. SMARCB1 knockdown/loss-of-function in hESCs; ChIP-seq; ATAC-seq; directed differentiation assays eLife High 31033435
2020 SMARCB1 loss in an inducible iPSC-based system interacts with neural differentiation state to cause resistance to terminal differentiation and defects in maintenance of normal cell state. The downstream effects of SMARCB1 loss are substantially different depending on the differentiation state of the cell. Inducible SMARCB1 loss-of-function in human iPSCs; directed neuronal differentiation; cerebral organoid differentiation; transcriptomic analysis Genes & development Medium 32912900
2020 SMARCB1 loss increases chromatin accessibility at the STAT3 locus in vitro, and SMARCB1 knockout cell lines show increased IL6/JAK/STAT3 signaling in orthotopic in vivo models. A pSTAT3 selective inhibitor (TTI-101) reduces tumor growth in SMARCB1 KO xenograft and patient-derived xenograft models, establishing the IL6/JAK/STAT3 axis as a SMARCB1-deficiency-driven vulnerability. SMARCB1 knockout; ATAC-seq; orthotopic xenograft models; pharmacological STAT3 inhibition; patient-derived xenograft Nature communications High 38355560
2020 SMARCB1 directly binds the IL6 promoter in a steady state (ChIP), dissociates during immune activation, and acts as a direct transcriptional repressor of IL6. Loss- and gain-of-function studies confirm that SMARCB1 represses IL6 expression and loss of SMARCB1 reduces cell cycle progression via p21 upregulation. ChIP; loss- and gain-of-function (siRNA and overexpression); transcriptome analysis; flow cytometry International journal of molecular sciences Medium 32492816
2020 SMARCB1 upregulation in liver cancer contributes to SWI/SNF complex stability. SMARCB1 binds the enhancer of NUP210 (Nucleoporin 210) and regulates H3K27Ac enrichment there, changing NUP210 downstream gene expression (including cholesterol homeostasis and xenobiotic metabolism). NUP210 acts as a key scaffold for SMARCB1 and P300 on chromatin. ChIP-seq for SMARCB1 and H3K27Ac; loss- and gain-of-function in liver cancer cells; in vivo tumor models Cancer research Medium 33239431
2021 NMR structure of the INI1/SMARCB1 Rpt1 domain and modeling of its interaction with the HIV-1 integrase C-terminal domain (IN-CTD) reveal that INI1-Rpt1 interface residues overlap with those required for IN/RNA interaction. INI1-Rpt1 and TAR RNA compete for IN binding with similar IC50 values. Computational modeling suggests INI1-Rpt1 structurally mimics TAR RNA at the interface, explaining how INI1 influences HIV-1 late events via integrase. NMR structure determination; mutational analysis; competition binding assays (IC50); computational modeling Nature communications High 33980829
2023 SMARCB1 re-expression in renal medullary carcinoma (RMC) cells reverses a TFCP2L1→MYC transcriptional switch, repressing MYC and NFE2L2-associated oncogenic and ferroptosis-resistance programs, leading to ferroptotic cell death. SMARCB1 loss activates MYC and ferroptosis resistance programs in TAL (thick ascending limb) cell-derived RMC, linking SCT-associated hypoxia and iron environment to SMARCB1-mediated transformation. Single-cell RNA-seq of human RMC; SMARCB1 re-expression with transcriptomic analysis; ferroptosis assays Nature communications High 37236926
2023 SMARCB1 loss in malignant rhabdoid tumors leads to dramatic reshaping of the regulatory landscape including patient-specific looping of distal enhancer regions with the MYC oncogene promoter (demonstrated by chromosome conformation capture). SMARCB1 reconstitution reverses this epigenetic reprogramming. Intertumoral heterogeneity in MYC enhancer utilization is present in patient tissues. Multi-omics on patient-derived MRT organoids; SMARCB1 re-expression; chromosome conformation capture (Hi-C/4C); single-cell RNA-seq; single-cell ATAC-seq on patient tissues Nature communications High 38040699
2023 Hypoxia induces SMARCB1 protein degradation in renal cells, protecting them from hypoxic stress. In a sickle cell trait mouse model, SMARCB1 wild-type renal tumors show lower SMARCB1 levels and more aggressive growth than controls; SMARCB1 reconstitution restores sensitivity to hypoxic stress in vitro and in vivo. In vitro hypoxia experiments; sickle cell trait mouse model; SMARCB1 re-expression; in vivo tumor growth assays Proceedings of the National Academy of Sciences of the United States of America Medium 37186844
2024 DCAF5 (a CUL4-DDB1 substrate receptor) functions as a quality-control factor for SWI/SNF complexes: in the absence of SMARCB1, DCAF5 promotes degradation of incompletely assembled (SMARCB1-deficient) SWI/SNF complexes. DCAF5 depletion allows SMARCB1-deficient SWI/SNF complexes to re-accumulate, rebind target chromatin loci, and restore SWI/SNF-mediated gene expression to levels sufficient to reverse the cancer state, including in vivo. Thus, SMARCB1-mutant cancer results not from loss of SMARCB1 function per se, but from DCAF5-mediated degradation of residual SWI/SNF complexes. Genome-wide CRISPR screen (Cancer Dependency Map); DCAF5 depletion; ChIP-seq; gene expression analysis; in vivo xenograft assays Nature High 38538798
2024 In SMARCB1-deficient cancers, SMARCB1 loss leads to localization of H3K27ac and recruitment of CBP and p300 acetyltransferases at the KREMEN2 locus (rather than H3K27me3/EZH2 seen in SMARCB1-intact cells), resulting in KREMEN2 transcriptional upregulation. Simultaneous inhibition of CBP/p300 downregulates KREMEN2 and induces apoptosis via KREMEN1 monomerization and suppression of anti-apoptotic signaling, selectively in SMARCB1-deficient cells. Dual siRNA paralog synthetic lethal screen; ChIP-seq for H3K27me3, H3K27ac, EZH2, CBP, p300; CBP/p300 inhibitor treatment; xenograft models; KREMEN2 functional studies Nature communications High 38839769

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer research 692 9892189
2020 Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. The Lancet. Oncology 328 33035459
2011 INI1-deficient tumors: diagnostic features and molecular genetics. The American journal of surgical pathology 319 21934399
2007 Germline mutation of INI1/SMARCB1 in familial schwannomatosis. American journal of human genetics 277 17357086
2011 Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatric blood & cancer 271 21108436
2005 SMARCB1/INI1 tumor suppressor gene is frequently inactivated in epithelioid sarcomas. Cancer research 262 15899790
2017 SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters. Nature genetics 226 28945250
1998 The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components of the SWI/SNF complex. Proceedings of the National Academy of Sciences of the United States of America 205 9539705
1995 The Drosophila snr1 and brm proteins are related to yeast SWI/SNF proteins and are components of a large protein complex. Molecular biology of the cell 199 7579694
2002 Cell cycle arrest and repression of cyclin D1 transcription by INI1/hSNF5. Molecular and cellular biology 194 12138206
2017 SMARCB1 (INI-1)-deficient Sinonasal Carcinoma: A Series of 39 Cases Expanding the Morphologic and Clinicopathologic Spectrum of a Recently Described Entity. The American journal of surgical pathology 188 28291122
2002 Re-expression of hSNF5/INI1/BAF47 in pediatric tumor cells leads to G1 arrest associated with induction of p16ink4a and activation of RB. Oncogene 173 12149641
2017 Oncogenic roles of SMARCB1/INI1 and its deficient tumors. Cancer science 164 28109176
2009 The role of SMARCB1/INI1 in development of rhabdoid tumor. Cancer biology & therapy 158 19305156
2014 SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract. The American journal of surgical pathology 153 25007146
2010 Loss of SMARCB1/INI1 expression in poorly differentiated chordomas. Acta neuropathologica 152 21057957
2008 Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis. Journal of medical genetics 152 18285426
2014 The expanding family of SMARCB1(INI1)-deficient neoplasia: implications of phenotypic, biological, and molecular heterogeneity. Advances in anatomic pathology 135 25299309
2014 SMARCB1(INI1)-deficient sinonasal basaloid carcinoma: a novel member of the expanding family of SMARCB1-deficient neoplasms. The American journal of surgical pathology 129 24832165
2014 Mechanisms by which SMARCB1 loss drives rhabdoid tumor growth. Cancer genetics 117 24853101
2008 Alterations in the SMARCB1 (INI1) tumor suppressor gene in familial schwannomatosis. Clinical genetics 116 18647326
2010 Reduced expression of SMARCB1/INI1 protein in synovial sarcoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 98 20305614
2014 SMARCB1 (INI1)-negative rhabdoid carcinomas of the gastrointestinal tract: clinicopathologic and molecular study of a highly aggressive variant with literature review. The American journal of surgical pathology 97 24503755
2017 SMARCB1-deficient Tumors of Childhood: A Practical Guide. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 91 29280680
2007 Immunohistochemistry of INI1 expression: a new tool for old challenges in CNS and soft tissue pathology. Advances in anatomic pathology 85 17717433
2023 Tazemetostat for tumors harboring SMARCB1/SMARCA4 or EZH2 alterations: results from NCI-COG pediatric MATCH APEC1621C. Journal of the National Cancer Institute 83 37228094
2017 Timing of Smarcb1 and Nf2 inactivation determines schwannoma versus rhabdoid tumor development. Nature communications 79 28824165
2014 SMARCB1 mutations in schwannomatosis and genotype correlations with rhabdoid tumors. Cancer genetics 79 24933152
1999 Alteration of hSNF5/INI1/BAF47 detected in rhabdoid cell lines and primary rhabdomyosarcomas but not Wilms' tumors. Oncogene 79 10602515
2004 The tumor suppressor hSNF5/INI1 modulates cell growth and actin cytoskeleton organization. Cancer research 76 15150092
2018 A Model Linking Sickle Cell Hemoglobinopathies and SMARCB1 Loss in Renal Medullary Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 71 29440190
2014 Pathology and diagnosis of SMARCB1-deficient tumors. Cancer genetics 66 25246033
2016 Gene of the month: SMARCB1. Journal of clinical pathology 63 26941181
2018 Anti-inflammatory and Antioxidant Properties of Probiotic Bacterium Lactobacillus mucosae AN1 and Lactobacillus fermentum SNR1 in Wistar Albino Rats. Frontiers in microbiology 62 30619149
2017 SMARCB1/INI1 Involvement in Pediatric Chordoma: A Mutational and Immunohistochemical Analysis. The American journal of surgical pathology 58 27635948
2012 p63, CK7, PAX8 and INI-1: an optimal immunohistochemical panel to distinguish poorly differentiated urothelial cell carcinoma from high-grade tumours of the renal collecting system. Histopathology 57 22260386
2018 SWI/SNF Chromatin-remodeling Complex Status in SMARCB1/INI1-preserved Epithelioid Sarcoma. The American journal of surgical pathology 55 29309303
2019 Recurrent SMARCB1 Inactivation in Epithelioid Malignant Peripheral Nerve Sheath Tumors. The American journal of surgical pathology 54 30864974
2018 SMARCB1 (INI1)-deficient sinonasal carcinoma: a series of 13 cases with assessment of histologic patterns. Human pathology 54 30120966
2017 SMARCB1/INI1 Loss in Epithelioid Schwannoma: A Clinicopathologic and Immunohistochemical Study of 65 Cases. The American journal of surgical pathology 53 28368924
2019 SMARCB1 (INI-1)-Deficient Adenocarcinoma of the Sinonasal Tract: A Potentially Under-Recognized form of Sinonasal Adenocarcinoma with Occasional Yolk Sac Tumor-Like Features. Head and neck pathology 51 31468350
2015 Reappraisal of sinonasal undifferentiated carcinoma: SMARCB1 (INI1)-deficient sinonasal carcinoma: a single-institution experience. Virchows Archiv : an international journal of pathology 51 26407663
2024 Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF. Nature 49 38538798
2003 SNR1 is an essential subunit in a subset of Drosophila brm complexes, targeting specific functions during development. Developmental biology 48 12645932
2012 Expression of SMARCB1 (INI1) mutations in familial schwannomatosis. Human molecular genetics 47 22949514
2002 Chromatin remodeling factor encoded by ini1 induces G1 arrest and apoptosis in ini1-deficient cells. Oncogene 44 12082626
2020 Genomic and Immunologic Characterization of INI1-Deficient Pediatric Cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 42 32122923
2020 SMARCB1 loss interacts with neuronal differentiation state to block maturation and impact cell stability. Genes & development 40 32912900
2013 SMARCB1/INI1 genetic inactivation is responsible for tumorigenic properties of epithelioid sarcoma cell line VAESBJ. Molecular cancer therapeutics 38 23576573
2011 Immunohistochemical analysis of SMARCB1/INI-1 expression in collecting duct carcinoma. Urology 38 21705046
2007 INI1 induces interferon signaling and spindle checkpoint in rhabdoid tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 37 17699849
2019 Tumor suppressor SMARCB1 suppresses super-enhancers to govern hESC lineage determination. eLife 35 31033435
2012 The chromatin remodeling and mRNA splicing functions of the Brahma (SWI/SNF) complex are mediated by the SNR1/SNF5 regulatory subunit. Nucleic acids research 35 22467207
2024 The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer. Nature communications 34 38355560
2003 The Drosophila SNR1 (SNF5/INI1) subunit directs essential developmental functions of the Brahma chromatin remodeling complex. Molecular and cellular biology 34 12482982
2006 HIV-1 replication in cell lines harboring INI1/hSNF5 mutations. Retrovirology 30 16945155
2000 HSNF5/INI1 gene mutations in lymphoid malignancy. Cancer genetics and cytogenetics 30 11104031
2023 SMARCB1 regulates a TFCP2L1-MYC transcriptional switch promoting renal medullary carcinoma transformation and ferroptosis resistance. Nature communications 29 37236926
2023 SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors. Nature communications 29 38040699
2019 Mutations in SMARCB1 and in other Coffin-Siris syndrome genes lead to various brain midline defects. Nature communications 29 31273213
2017 Structural Insights into BAF47 and BAF155 Complex Formation. Journal of molecular biology 29 28438634
2015 Utility of characteristic 'Weak to Absent' INI1/SMARCB1/BAF47 expression in diagnosis of synovial sarcomas. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 29 25912315
2013 Structural and functional role of INI1 and LEDGF in the HIV-1 preintegration complex. PloS one 29 23593299
2013 Loss of IGFBP7 expression and persistent AKT activation contribute to SMARCB1/Snf5-mediated tumorigenesis. Oncogene 29 23851500
2009 INI1 and GLUT-1 expression in epithelioid sarcoma and its cutaneous neoplastic and nonneoplastic mimics. The American Journal of dermatopathology 29 19318800
2020 Nucleoporin 210 Serves a Key Scaffold for SMARCB1 in Liver Cancer. Cancer research 27 33239431
2020 SMARCB1/INI1-deficient tumors of adulthood. F1000Research 25 33796273
2009 Multimerization and DNA binding properties of INI1/hSNF5 and its functional significance. The Journal of biological chemistry 24 19398554
2023 SMARCB1 regulates the hypoxic stress response in sickle cell trait. Proceedings of the National Academy of Sciences of the United States of America 23 37186844
2022 The genetic landscape of SMARCB1 alterations in SMARCB1-deficient spectrum of mesenchymal neoplasms. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 23 36088476
2006 dDYRK2 and Minibrain interact with the chromatin remodelling factors SNR1 and TRX. The Biochemical journal 23 16671894
2004 SNR1 (INI1/SNF5) mediates important cell growth functions of the Drosophila Brahma (SWI/SNF) chromatin remodeling complex. Genetics 23 15454538
2012 Specificity and sensitivity of INI-1 labeling in epithelioid sarcoma. Loss of INI1 expression as a frequent immunohistochemical event in synovial sarcoma. Polish journal of pathology : official journal of the Polish Society of Pathologists 21 23161234
2020 Genetic basis of SMARCB1 protein loss in 22 sinonasal carcinomas. Human pathology 20 32818509
2020 BRG1, INI1, and ARID1B Deficiency in Endometrial Carcinoma: A Clinicopathologic and Immunohistochemical Analysis of a Large Series From a Single Institution. The American journal of surgical pathology 20 32910019
2014 The SWI/SNF subunit/tumor suppressor BAF47/INI1 is essential in cell cycle arrest upon skeletal muscle terminal differentiation. PloS one 20 25271443
2006 SMARCB1/INI1 missense mutation in mucinous carcinoma with rhabdoid features. Pathology international 20 17040295
2022 Vulvar Yolk Sac Tumors Are Somatically Derived SMARCB1 (INI-1)-Deficient Neoplasms. The American journal of surgical pathology 19 34265804
2021 Case Report: SMARCB1 (INI-1)-Deficient Carcinoma of the Nasal Cavity with Pure Yolk Sac Tumor Differentiation and Elevated Serum AFP Levels. OncoTargets and therapy 19 33824593
2021 INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication. Nature communications 19 33980829
2020 SMARCB1/INI1 Deficient Sino-Nasal Carcinoma: Extending the Histomorphological Features. Head and neck pathology 19 33141418
2016 Cytopathologic characteristics of SMARCB1 (INI-1) deficient sinonasal carcinoma: A potential diagnostic pitfall. Diagnostic cytopathology 19 27177850
2009 The role of INI1/hSNF5 in gene regulation and cancer. Biochemistry and cell biology = Biochimie et biologie cellulaire 19 19234532
2023 Targeting EZH2 in SMARCB1-deficient sarcomas: Advances and opportunities to potentiate the efficacy of EZH2 inhibitors. Biochemical pharmacology 18 37541451
2022 Molecular and immunophenotypic characterization of SMARCB1 (INI1) - deficient intrathoracic Neoplasms. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 18 35864317
2020 INI-1 (SMARCB1)-Deficient Undifferentiated Sinonasal Carcinoma: Novel Paradigm of Molecular Testing in the Diagnosis and Management of Sinonasal Malignancies. The oncologist 18 32337786
2016 The SWI/SNF Complex Protein Snr1 Is a Tumor Suppressor in Drosophila Imaginal Tissues. Cancer research 18 27923836
2022 SMARCB1 (INI1)-Deficient Sinonasal Carcinoma with Yolk Sac differentiation Showing Co-loss of SMARCA4 Immunostaining - A Case Report and Literature Review. Head and neck pathology 17 35257325
2021 Recurrent loss of chromosome 22 and SMARCB1 deletion in extra-axial chordoma: A clinicopathological and molecular analysis. Genes, chromosomes & cancer 17 34392582
2017 Targeting Polo-like kinase 1 in SMARCB1 deleted atypical teratoid rhabdoid tumor. Oncotarget 17 29228610
2018 Cytopathologic features of SMARCB1 (INI-1)-deficient sinonasal carcinoma. Cancer cytopathology 15 29797680
1995 HIV integration. Ini1 for integration? Current biology : CB 15 7627549
2022 Synergistic action of WDR5 and HDM2 inhibitors in SMARCB1-deficient cancer cells. NAR cancer 14 35252869
2022 Primary adult sellar SMARCB1/INI1-deficient tumor represents a subtype of atypical teratoid/rhabdoid tumor. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 14 35804041
2024 Targeting dependency on a paralog pair of CBP/p300 against de-repression of KREMEN2 in SMARCB1-deficient cancers. Nature communications 13 38839769
2021 SMARCA4 (BRG1) and SMARCB1 (INI1) expression in TTF-1 negative neuroendocrine carcinomas including merkel cell carcinoma. Pathology, research and practice 13 33581550
2017 EWSR1-fusion-negative, SMARCB1-deficient primary pulmonary myxoid sarcoma. Polish journal of pathology : official journal of the Polish Society of Pathologists 13 29363919
2020 SMARCB1 Acts as a Quiescent Gatekeeper for Cell Cycle and Immune Response in Human Cells. International journal of molecular sciences 12 32492816
2020 SMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinoma mimicking solid pseudopapillary neoplasm: A case report and review of the literature. World journal of gastroenterology 12 33024402
2018 SMARCB1/INI1/BAF47- deficient pleural malignant mesothelioma with rhabdoid features. Pathology international 11 29316066

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