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
2026-04-28
100 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMARCB1 (INI1/SNF5/BAF47) is a core subunit of SWI/SNF (BAF/PBAF) chromatin-remodeling complexes that functions as a tumor suppressor by stabilizing complex occupancy on chromatin, activating enhancers, opposing Polycomb-mediated repression, and governing cell cycle exit and terminal differentiation. SMARCB1 loss does not disassemble SWI/SNF complexes but instead triggers DCAF5-mediated proteasomal degradation of the incompletely assembled complexes, collapsing BAF-dependent enhancer landscapes and de-repressing MYC target genes—partly through relief of a direct, chromatin-remodeling-independent inhibition of MYC DNA binding—while also activating cyclin D1 (via loss of HDAC1 recruitment to its promoter), PI3K/AKT, and IL6/JAK/STAT3 oncogenic pathways (PMID:28945250, PMID:38538798, PMID:31043611, PMID:12138206, PMID:23851500, PMID:38355560). Biallelic SMARCB1 inactivation causes malignant rhabdoid tumors in which the specific tumor type is determined by the developmental stage at which loss occurs, and SMARCB1 is essential for neural lineage differentiation from embryonic and induced pluripotent stem cells (PMID:28824165, PMID:31033435, PMID:32912900). Its nuclear localization is regulated by a CRM1-dependent nuclear export signal in the Repeat 2 domain that is normally masked; disease-associated truncations unmask this NES and abolish tumor-suppressor activity (PMID:11782423).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1999 High

    The question of how SWI/SNF participates in MYC-driven transcription was answered by demonstrating that c-MYC physically binds INI1 through the bHLH-Zip and Rpt1 domains, and that BRG1 ATPase activity is required for MYC transactivation, establishing SWI/SNF as a direct MYC coactivator.

    Evidence Yeast two-hybrid, in vitro binding, co-IP, and dominant-negative BRG1 transactivation assay in mammalian cells

    PMID:10319872

    Open questions at the time
    • Whether INI1 facilitates or restrains MYC activity at endogenous loci was not resolved
    • Genome-wide MYC target analysis was not performed
  2. 2001 High

    The in vivo tumor-suppressor identity of Ini1 was established: homozygous loss causes peri-implantation lethality and heterozygotes develop tumors with LOH, answering whether SMARCB1 is a bona fide two-hit tumor suppressor.

    Evidence Conditional knockout mouse model with embryo culture and LOH analysis of tumors

    PMID:11313485

    Open questions at the time
    • Cell-type-of-origin for tumors was unknown
    • Mechanism linking Ini1 loss to transformation was unresolved
  3. 2002 High

    Three key mechanistic properties of INI1 were defined simultaneously: (1) it recruits HDAC1 to repress cyclin D1 transcription, explaining cell cycle arrest; (2) its Repeat 1 and Repeat 2 domains are required for growth suppression; and (3) a CRM1-dependent NES in Repeat 2 is normally masked, and disease truncations that unmask it cause cytoplasmic mislocalization and loss of function.

    Evidence ChIP for HDAC1 at cyclin D1 promoter with cyclin D1 rescue, adenoviral re-expression with domain deletions, NES mutagenesis with leptomycin B rescue and immunofluorescence

    PMID:11782423 PMID:12082626 PMID:12138206

    Open questions at the time
    • Whether HDAC1 recruitment is direct or through intermediaries was not fully dissected
    • Structural basis of NES masking was unknown
  4. 2004 High

    Genome-wide target gene identification revealed that INI1 directly regulates cytoskeletal remodeling through Rho GTPase suppression and represses DNA replication genes, broadening its role beyond cell cycle control; separately, INI1 was shown to be specifically incorporated into HIV-1 virions via its S6 domain interaction with integrase.

    Evidence Inducible INI1 system with microarray profiling and ER-fusion for direct-target discrimination; virion purification with stoichiometric analysis and trans-dominant mutant specificity across retroviruses

    PMID:14963118 PMID:15150092

    Open questions at the time
    • Functional significance of INI1 in virions for HIV-1 replication cycle was not resolved
    • Direct chromatin targets mediating Rho suppression were not identified
  5. 2009 Medium

    The coupling of SWI/SNF to histone methyltransferase complexes was established by showing that INI1 directly binds the SET domains of MLL3/MLL4, enabling mutual recruitment to nuclear receptor target genes and cooperative transactivation.

    Evidence Co-IP, GST pulldown, ChIP at NR target genes, and mutational analysis of the interaction interface

    PMID:19221051

    Open questions at the time
    • Genome-wide co-occupancy of SWI/SNF and ASCOM was not mapped
    • Whether the interaction is constitutive or signal-regulated was unclear
  6. 2014 Medium

    SMARCB1's role in terminal differentiation was extended to skeletal muscle: BAF47 interacts with MyoD and shifts between SWI/SNF and N-CoR-1 repressor complexes during differentiation, and is specifically required for irreversible cell cycle exit in myoblasts.

    Evidence Co-IP of MyoD with SWI/SNF subunits, RNAi knockdown, and myogenic differentiation assays

    PMID:25271443

    Open questions at the time
    • Whether BAF47 directly bridges MyoD to N-CoR-1 was not resolved
    • In vivo muscle phenotype of Smarcb1 loss was not tested
  7. 2017 High

    Three advances converged to redefine SMARCB1's chromatin mechanism and developmental role: (1) SMARCB1 stabilizes BAF complex occupancy genome-wide without affecting complex assembly, activating enhancers and opposing Polycomb; (2) the crystal structure of BAF47 RPT1 bound to BAF155 SWIRM defined the core incorporation interface; (3) developmental timing of Smarcb1 loss determines tumor type (rhabdoid vs. schwannoma).

    Evidence ChIP-seq/ATAC-seq in isogenic rescue system; X-ray crystallography with ITC and NMR validation; stage-specific conditional KO mice with molecular profiling

    PMID:28438634 PMID:28824165 PMID:28945250

    Open questions at the time
    • Structural basis for how SMARCB1 stabilizes BAF on chromatin was not determined
    • Whether BAF vs. PBAF complexes are differentially affected by timing of loss was not resolved
  8. 2019 High

    Multiple studies revealed that SMARCB1 has a chromatin-remodeling-independent function: it directly inhibits MYC DNA binding genome-wide, and this MYC-inhibitory activity is separable from its role in SWI/SNF-mediated chromatin remodeling; concurrently, SMARCB1 was shown to be required specifically for neural induction in hESCs and to regulate super-enhancer accessibility, while SMARCB1-loss cancers exhibit synthetic lethality with UBE2C and proteasome inhibition.

    Evidence Biochemical DNA-binding assays plus ChIP-seq/RNA-seq with domain separation; SMARCB1 KD in hESCs with directed differentiation and ATAC-seq; CRISPR/RNAi screens in patient-derived RMC models with proteasome inhibitor treatment

    PMID:30860482 PMID:31033435 PMID:31043611

    Open questions at the time
    • Structural basis of SNF5-mediated MYC inhibition was unknown
    • Whether super-enhancer regulation is a general or neural-specific function was not tested
  9. 2020 Medium

    SMARCB1 loss was shown to block terminal neuronal differentiation in iPSC-derived neural stem cells, with context-dependent downstream effects varying by differentiation state, and separately, SMARCB1 deficiency in liver cancer was linked to NUP210-dependent enhancer rewiring and P300 scaffolding.

    Evidence Inducible SMARCB1 KO in human iPSCs with directed neuronal differentiation; ChIP-seq and xenograft studies in liver cancer cells

    PMID:32912900 PMID:33239431

    Open questions at the time
    • Whether NUP210 scaffolding function is relevant outside liver cancer was not tested
    • Organoid models did not fully recapitulate in vivo rhabdoid tumorigenesis
  10. 2021 High

    Two discoveries expanded the oncogenic consequences of SMARCB1 loss: (1) in synovial sarcoma, the SS18-SSX fusion co-incorporates with SMARCB1 into CBAF and drives whole-complex degradation, shifting the BAF landscape toward PBAF/GBAF; (2) SMARCB1 loss de-represses endogenous retrovirus HERV-K (HML-2), activating RAS/MAPK signaling in AT/RT cells.

    Evidence Co-IP/mass spectrometry with reconstituted CBAF, mouse genetic models with ChIP-seq; ChIP at HML-2 promoter with CRISPR-dCas9 suppression and RNAi-rescue experiments

    PMID:34078620 PMID:34145313

    Open questions at the time
    • Whether HERV-K de-repression is a universal feature of SMARCB1-null tumors was not established
    • The relative contributions of CBAF degradation vs. SMARCB1 protein reduction in synovial sarcoma were not quantitatively separated
  11. 2023 High

    Patient-level regulatory heterogeneity was revealed: SMARCB1 loss activates patient-specific distal enhancer-to-MYC promoter loops in malignant rhabdoid tumors; separately, SMARCB1 loss was shown to activate ferroptosis resistance via NFE2L2 programs, and hypoxia-induced SMARCB1 degradation was identified as a renal-protective mechanism exploited by SMARCB1-null tumors to resist angiogenesis inhibition.

    Evidence Multi-omics (Hi-C, ChIP-seq, ATAC-seq, scRNA-seq) in patient-derived MRT organoids; ferroptosis assays with SMARCB1 reconstitution; hypoxia treatment with protein stability assays and in vivo xenograft models

    PMID:37186844 PMID:37236926 PMID:38040699

    Open questions at the time
    • Whether patient-specific enhancer loops are therapeutically targetable was not tested
    • The E3 ligase mediating hypoxia-induced SMARCB1 degradation was not identified
  12. 2024 High

    The central mechanism of SMARCB1-mutant oncogenesis was redefined: DCAF5 (a DDB1-CUL4 substrate receptor) degrades incompletely assembled SWI/SNF complexes lacking SMARCB1; DCAF5 depletion allows SMARCB1-deficient complexes to re-accumulate on chromatin and restore gene expression, reversing the cancer state in vivo—establishing that tumorigenesis results from complex degradation rather than direct loss of SMARCB1 function; separately, SMARCB1 loss in bladder cancer activates IL6/JAK/STAT3 signaling via increased chromatin accessibility at the STAT3 locus.

    Evidence Near genome-wide CRISPR screens across 14 SMARCB1-mutant lines, biochemical reconstitution, ChIP-seq, RNA-seq, in vivo xenograft rescue; SMARCB1 CRISPR KO in bladder cancer with ATAC-seq, orthotopic xenograft, and STAT3 inhibitor treatment

    PMID:38355560 PMID:38538798

    Open questions at the time
    • Whether DCAF5 directly recognizes a degron exposed by SMARCB1 absence or senses an assembly intermediate is unknown
    • Whether DCAF5 inhibition could serve as a therapeutic strategy in patients has not been tested clinically

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis by which SMARCB1 prevents DCAF5 recognition of SWI/SNF complexes, the mechanism by which SMARCB1 inhibits MYC DNA binding at the atomic level, whether therapeutic DCAF5 inhibition can substitute for SMARCB1 restoration in patients, and whether the diverse downstream pathways (MYC, Polycomb, STAT3, PI3K/AKT, ferroptosis resistance) converge on a unified oncogenic program or represent tissue-specific outputs.
  • No structural model of DCAF5-SWI/SNF recognition exists
  • No clinical data on DCAF5-targeted therapy
  • Integration of tissue-specific tumor programs remains undone

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 4 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-1643685 Disease 5 R-HSA-1640170 Cell Cycle 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3
Partners
BAF155BRG1DCAF5HDAC1MLL3MLL4MYCMYOD
Complex memberships
N-CoR-1 repressor complexPBAFSWI/SNF (BAF)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 c-MYC physically interacts with INI1/hSNF5 both in vitro and in vivo; the c-MYC bHLH-Zip domain and INI1 Repeat 1 (Rpt1) region are required for this interaction, and the SWI/SNF complex (including its ATPase BRG1) is necessary for c-MYC-mediated transactivation. Yeast two-hybrid screen, in vitro binding assay, co-immunoprecipitation, dominant-negative BRG1 transactivation assay Nature genetics High 10319872
2001 Homozygous Ini1 deletion in mice causes peri-implantation lethality (embryos die 3.5–5.5 dpc), and heterozygous Ini1 mice develop tumors with loss of the second allele, establishing Ini1 as a bona fide tumor suppressor in vivo. Conditional knockout mouse model, embryo culture, tumor analysis with LOH at Ini1 locus Molecular and cellular biology High 11313485
2002 INI1/hSNF5 reintroduction into AT/RT-derived cell lines causes G0-G1 arrest and flat cell formation by directly recruiting HDAC1 to the cyclin D1 promoter, deacetylating histones there and repressing cyclin D1 transcription; re-expression of cyclin D1 from a heterologous promoter rescues the arrest. Tetracycline-inducible expression, chromatin immunoprecipitation (ChIP), HDAC inhibitor treatment, cyclin D1 rescue experiment, flow cytometry Molecular and cellular biology High 12138206
2002 INI1/hSNF5 contains a nuclear export signal (NES) in its conserved Repeat 2 domain that is normally masked by a downstream sequence; upon deletion of that sequence (as found in MRT mutant INI1(1-319 delG950)), the NES is unmasked, the protein mislocalizes to the cytoplasm via hCRM1/exportin1, and it loses tumor-suppressor function (cell cycle arrest); disrupting the NES in the mutant restores nuclear localization and cell cycle arrest. NES mutational analysis, leptomycin B treatment, co-IP of INI1 with hCRM1 in vivo and in vitro, subcellular fractionation/immunofluorescence, flat-cell formation assay The EMBO journal High 11782423
2002 Re-expression of INI1 in INI1-deficient cell lines induces G1 arrest and apoptosis; deletion analysis shows that Repeat 1 and Repeat 2 domains of INI1 are required for growth suppression. Recombinant adenovirus-mediated overexpression, colony formation assay, flow cytometry, BrdU incorporation, PARP cleavage assay Oncogene Medium 12082626
2004 hSNF5/INI1 induction causes G1 arrest (reversible), down-regulates DNA replication complex components, and reorganizes the actin cytoskeleton by disrupting stress fibers and focal adhesions via suppression of Rho GTPase activity; genome-wide transcriptional profiling identified direct target genes acting independently of de novo protein synthesis. Tetracycline-inducible hSNF5/INI1 system, cDNA microarray (22,000 genes), estrogen-receptor fusion protein to identify direct targets, Rho activity assay, immunofluorescence of actin/focal adhesions Cancer research High 15150092
2004 INI1/hSNF5 is specifically incorporated into HIV-1 virions (integrase:INI1 stoichiometry ~2:1 molar ratio) through a direct interaction with HIV-1 integrase mediated by the INI1 S6 domain; INI1 is absent from purified microvesicles and not incorporated into other retroviral particles, and the INI1 S6 transdominant mutant specifically blocks HIV-1 but not other retroviral particle production. Virion purification and quantitative western blotting, microvesicle fractionation, co-IP with integrase, transdominant mutant inhibition assay across multiple retroviruses Journal of virology High 14963118
2007 INI1 reintroduction into rhabdoid cells activates interferon-stimulated genes (causing G1 arrest and flat cell formation) and represses mitotic genes including PLK1; RNAi knockdown of PLK1 in rhabdoid cells causes mitotic arrest, aberrant nuclear division, and apoptosis, identifying PLK1 as a functionally important downstream target of INI1. cDNA microarray in rhabdoid cells, qRT-PCR, western blotting, IHC on primary tumors, RNA interference knockdown of PLK1, flow cytometry, apoptosis assays Clinical cancer research Medium 17699849
2009 The SET domains of MLL3 and MLL4 directly interact with INI1 (a SWI/SNF subunit), coupling the ASCOM histone H3K4 methyltransferase complex and the SWI/SNF chromatin-remodeling complex; this protein–protein interaction is required for mutual recruitment of both complexes to nuclear receptor target genes and for efficient nuclear receptor transactivation. Co-immunoprecipitation, GST pulldown, ChIP on NR target genes, mutational analysis of MLL3/4 SET domain and INI1 interaction interface Molecular endocrinology Medium 19221051
2013 SMARCB1/Snf5 re-expression in Smarcb1-deficient tumor cells restores sensitivity to apoptosis and abolishes xenograft growth; Smarcb1 loss is linked to persistent PI3K/AKT activation and loss of IGFBP7 transcription—re-introduction of IGFBP7 alone inhibits tumor development, and AKT inhibition blocks proliferation of Smarcb1-deficient cells. Smarcb1 re-expression in mouse tumor-derived cells, xenograft assay, AKT inhibitor treatment in vitro and in vivo, Igfbp7 re-expression experiment, gene expression profiling Oncogene Medium 23851500
2017 SMARCB1 (BAF47) loss destabilizes BAF complexes on chromatin without disrupting overall complex assembly or integrity; restoration of SMARCB1 in BAF47-deficient sarcoma cells increases genome-wide BAF occupancy, activates enhancers broadly, and opposes Polycomb-mediated repression at bivalent promoters; BAF and PBAF complexes differentially regulate enhancers and promoters, respectively. ChIP-seq for BAF complex subunits and histone marks before/after SMARCB1 rescue, ATAC-seq, genome-wide occupancy analysis in isogenic cell lines Nature genetics High 28945250
2017 Crystal structure of BAF47 (SMARCB1) Repeat 1 (RPT1) domain in complex with the SWIRM domain of BAF155 was determined; mutagenesis, isothermal titration calorimetry, and NMR titrations confirm that the BAF155 SWIRM domain mediates direct interaction with BAF47 RPT1, forming a core complex module. X-ray crystallography, ITC, NMR titration, mutagenesis Journal of molecular biology High 28438634
2017 Early loss of Smarcb1 in neural crest cells initiates rhabdoid tumor formation in cranial nerves/meninges, whereas Smarcb1 loss at a later developmental stage in the Schwann cell lineage combined with biallelic Nf2 inactivation generates schwannomas; timing of Smarcb1 loss determines tumor type. Tissue- and stage-specific conditional knockout mice, histological and molecular profiling of tumors, comparison with human tumor profiles Nature communications High 28824165
2019 SNF5 (SMARCB1) inhibits the DNA-binding ability of MYC and impedes genome-wide target gene recognition by MYC; this MYC-inhibitory function is separable from SNF5's role in chromatin remodeling; reintroduction of SNF5 into SMARCB1-null cells mimics the primary transcriptional effects of MYC inhibition. Biochemical DNA-binding assays, ChIP-seq for MYC occupancy before/after SNF5 reintroduction, RNA-seq, domain separation experiments distinguishing chromatin remodeling from MYC inhibition Nature communications High 31043611
2019 SMARCB1 is required in human embryonic stem cells (hESCs) specifically for neural induction but not mesodermal or endodermal differentiation; SMARCB1 represses bivalent genes and antagonizes chromatin accessibility at super-enhancers in hESCs, with an essential role in super-enhancer silencing during neural differentiation. SMARCB1 knockdown in hESCs, directed differentiation assays (neural, mesodermal, endodermal), ATAC-seq, ChIP-seq for histone marks and SMARCB1 occupancy eLife High 31033435
2019 SMARCB1 loss is required for survival of renal medullary carcinoma (RMC) cells; RMC depends on the ubiquitin-proteasome system (UPS), and proteasome inhibition causes G2/M arrest due to constitutive cyclin B1 accumulation; the E2 ubiquitin-conjugating enzyme UBE2C is essential across SMARCB1-loss cancers, defining a synthetic lethal relationship. Patient-derived RMC models, whole-genome sequencing identifying intronic SMARCB1 fusion, RNAi/CRISPR loss-of-function screens, small-molecule screen, proteasome inhibitor treatment, cell cycle analysis eLife High 30860482
2020 SMARCB1 loss in neural stem cells (iPSC-derived) blocks terminal neuronal differentiation and destabilizes normal cell state; the downstream effects of SMARCB1 loss differ substantially depending on the differentiation state of the cell at the time of loss. Inducible SMARCB1 loss-of-function system in human iPSCs, directed neuronal differentiation and cerebral organoid formation, transcriptional profiling Genes & development Medium 32912900
2021 SMARCB1 is incorporated into both PBAF and canonical BAF (CBAF) complexes in synovial sarcoma cells; SS18-SSX co-incorporates with SMARCB1 into CBAF but drives whole-complex degradation of CBAF, reducing SMARCB1 protein levels and shifting relative abundance toward PBAF and GBAF; combined Smarcb1 loss with SS18-SSX expression in mice produces tumors with distinct histomorphology and genome-wide BAF distributions. Co-IP/mass spectrometry identifying BAF subunit composition, recombinant CBAF reconstitution in human cells, mouse genetic models (Smarcb1 silencing + SS18-SSX expression), ChIP-seq for BAF complex distribution, RNA-seq Cancer discovery High 34078620
2023 SMARCB1 re-expression in renal medullary carcinoma cells reverses a MYC-driven oncogenic transcriptional program and a TFCP2L1-to-MYC switch; SMARCB1 loss also activates NFE2L2-associated ferroptosis resistance programs; SMARCB1 re-expression restores ferroptotic cell death. Single-cell RNA-seq of human RMC, SMARCB1 re-expression experiments, transcriptional profiling, ferroptosis assays Nature communications Medium 37236926
2023 Hypoxia induces SMARCB1 protein degradation in renal cells, protecting them from hypoxic stress; SMARCB1-null renal tumors are refractory to angiogenesis inhibition (hypoxia-inducing therapy), and reconstitution of SMARCB1 restores sensitivity to hypoxic stress in vitro and in vivo. Hypoxia treatment of renal cell lines, SMARCB1 protein stability assays, sickle cell trait mouse model (HbS knock-in), xenograft experiments with angiogenesis inhibitors, SMARCB1 reconstitution in vivo Proceedings of the National Academy of Sciences of the United States of America Medium 37186844
2024 DCAF5, a DDB1-CUL4 associated factor, promotes degradation of incompletely assembled SWI/SNF complexes that lack SMARCB1; depletion of DCAF5 in SMARCB1-mutant cancer cells allows SMARCB1-deficient SWI/SNF complexes to reaccumulate, rebind target loci, and restore SWI/SNF-mediated gene expression sufficient to reverse the cancer state, including in vivo—demonstrating that SMARCB1-mutant cancer results from DCAF5-mediated complex degradation rather than direct loss of SMARCB1 function. Near genome-wide CRISPR screen in 14 SMARCB1-mutant cell lines, DCAF5 depletion biochemical characterization, ChIP-seq, RNA-seq, in vivo xenograft rescue experiments Nature High 38538798
2024 SMARCB1 loss in bladder cancer increases chromatin accessibility at the STAT3 locus and activates the IL6/JAK/STAT3 signaling axis; orthotopic SMARCB1-knockout tumors show increased growth and metastasis, and selective pSTAT3 inhibition (TTI-101) reduces tumor growth in SMARCB1-KO xenografts and patient-derived xenograft models. SMARCB1 CRISPR KO in bladder cancer cell lines, ATAC-seq, orthotopic xenograft and PDX models, STAT3 inhibitor treatment, RNA-seq Nature communications Medium 38355560
2014 BAF47 (SMARCB1) is essential for cell cycle arrest during skeletal muscle terminal differentiation; BAF47 interacts with MyoD, is present in both SWI/SNF and N-CoR-1 repressor complexes in proliferating myoblasts, and shifts toward N-CoR-1 upon differentiation; unlike BRG1, BAF47 is specifically required for irreversible myoblast cell cycle exit. Co-immunoprecipitation of MyoD with SWI/SNF subunits, RNAi knockdown of BAF47/BRG1/BAF53a, myogenic differentiation assays, complex fractionation PloS one Medium 25271443
2021 SMARCB1 deletion in AT/RT cells leads to upregulation of Human Endogenous Retrovirus K (HERV-K/HML-2); SMARCB1 binds adjacent to the HML-2 promoter and represses its transcription; restoration of SMARCB1 downregulates HML-2 expression; HML-2 knockdown decreases RAS/MAPK signaling and reduces proliferation, placing SMARCB1-mediated HML-2 repression upstream of an oncogenic signaling pathway. ChIP (SMARCB1 binding at HML-2 promoter), SMARCB1 knockdown in neural stem cells, SMARCB1 re-expression in AT/RT lines, CRISPR-dCas9 HML-2 suppression, RNAi knockdown, NRAS overexpression rescue, qRT-PCR Scientific reports Medium 34145313
2023 SMARCB1 loss in malignant rhabdoid tumors activates patient-specific distal enhancer-to-MYC promoter loops; SMARCB1 reconstitution in patient-derived MRT organoids dramatically reshapes the regulatory landscape; chromosome conformation capture reveals patient-specific looping of distal enhancers to the MYC promoter, with heterogeneity confirmed by single-cell RNA-seq and ATAC-seq in patient tissues. SMARCB1 reconstitution in patient-derived MRT organoids, multi-omics (ChIP-seq, ATAC-seq, Hi-C/chromosome conformation capture), single-cell RNA-seq and ATAC-seq on patient tissues Nature communications High 38040699
2020 SMARCB1 loss in liver cancer cells promotes NUP210 (Nucleoporin 210) expression by binding to the NUP210 enhancer and increasing H3K27Ac enrichment there; NUP210 acts as a scaffold for SMARCB1 and the acetyltransferase P300 at chromatin, and SMARCB1 deficiency confers sensitivity to doxorubicin and P300 inhibitors. SMARCB1 loss/gain-of-function in liver cell lines, ChIP-seq for SMARCB1 and H3K27Ac, in vivo xenograft, pharmacological inhibitor studies Cancer research Medium 33239431

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 689 9892189
2009 Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. The American journal of surgical pathology 425 19033866
1999 Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. American journal of human genetics 323 10521299
2020 Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. The Lancet. Oncology 319 33035459
2011 INI1-deficient tumors: diagnostic features and molecular genetics. The American journal of surgical pathology 318 21934399
1999 c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function. Nature genetics 318 10319872
2007 Germline mutation of INI1/SMARCB1 in familial schwannomatosis. American journal of human genetics 276 17357086
2004 Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms. The American journal of surgical pathology 276 15105654
2011 Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatric blood & cancer 269 21108436
2005 SMARCB1/INI1 tumor suppressor gene is frequently inactivated in epithelioid sarcomas. Cancer research 260 15899790
2001 Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice. Molecular and cellular biology 244 11313485
2017 SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters. Nature genetics 223 28945250
2002 Cell cycle arrest and repression of cyclin D1 transcription by INI1/hSNF5. Molecular and cellular biology 194 12138206
2017 Oncogenic roles of SMARCB1/INI1 and its deficient tumors. Cancer science 162 28109176
2009 The role of SMARCB1/INI1 in development of rhabdoid tumor. Cancer biology & therapy 158 19305156
2008 Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis. Journal of medical genetics 152 18285426
2014 SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract. The American journal of surgical pathology 150 25007146
2010 Loss of SMARCB1/INI1 expression in poorly differentiated chordomas. Acta neuropathologica 149 21057957
2014 The expanding family of SMARCB1(INI1)-deficient neoplasia: implications of phenotypic, biological, and molecular heterogeneity. Advances in anatomic pathology 134 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 128 24832165
2008 Alterations in the SMARCB1 (INI1) tumor suppressor gene in familial schwannomatosis. Clinical genetics 116 18647326
2014 Mechanisms by which SMARCB1 loss drives rhabdoid tumor growth. Cancer genetics 114 24853101
2010 Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas. Journal of medical genetics 112 20930055
2007 hSNF5/INI1-deficient tumours and rhabdoid tumours are convergent but not fully overlapping entities. The Journal of pathology 103 17152049
2015 Pattern of SMARCB1 (INI1) and SMARCA4 (BRG1) in poorly differentiated endometrioid adenocarcinoma of the uterus: analysis of a series with emphasis on a novel SMARCA4-deficient dedifferentiated rhabdoid variant. Annals of diagnostic pathology 102 25920939
2011 Germline SMARCB1 mutation predisposes to multiple meningiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri. Neurogenetics 98 22038540
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 96 24503755
2014 Pancreatic undifferentiated rhabdoid carcinoma: KRAS alterations and SMARCB1 expression status define two subtypes. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 92 25103069
2008 Infrequent SMARCB1/INI1 gene alteration in epithelioid sarcoma: a useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor. Human pathology 91 18973917
2002 A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis. The EMBO journal 87 11782423
2007 Immunohistochemistry of INI1 expression: a new tool for old challenges in CNS and soft tissue pathology. Advances in anatomic pathology 84 17717433
2015 Balanced Translocations Disrupting SMARCB1 Are Hallmark Recurrent Genetic Alterations in Renal Medullary Carcinomas. European urology 82 26433572
2012 Frequency of SMARCB1 mutations in familial and sporadic schwannomatosis. Neurogenetics 80 22434358
2014 SMARCB1 mutations in schwannomatosis and genotype correlations with rhabdoid tumors. Cancer genetics 79 24933152
2017 Timing of Smarcb1 and Nf2 inactivation determines schwannoma versus rhabdoid tumor development. Nature communications 78 28824165
1999 Alteration of hSNF5/INI1/BAF47 detected in rhabdoid cell lines and primary rhabdomyosarcomas but not Wilms' tumors. Oncogene 78 10602515
2004 The tumor suppressor hSNF5/INI1 modulates cell growth and actin cytoskeleton organization. Cancer research 76 15150092
2023 Tazemetostat for tumors harboring SMARCB1/SMARCA4 or EZH2 alterations: results from NCI-COG pediatric MATCH APEC1621C. Journal of the National Cancer Institute 73 37228094
2019 Inhibition of MYC by the SMARCB1 tumor suppressor. Nature communications 67 31043611
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 67 29440190
2020 Atypical teratoid/rhabdoid tumors (ATRTs) with SMARCA4 mutation are molecularly distinct from SMARCB1-deficient cases. Acta neuropathologica 66 33331994
2014 Pathology and diagnosis of SMARCB1-deficient tumors. Cancer genetics 66 25246033
2016 Gene of the month: SMARCB1. Journal of clinical pathology 63 26941181
2004 Specificity of interaction of INI1/hSNF5 with retroviral integrases and its functional significance. Journal of virology 62 14963118
2018 Anti-inflammatory and Antioxidant Properties of Probiotic Bacterium Lactobacillus mucosae AN1 and Lactobacillus fermentum SNR1 in Wistar Albino Rats. Frontiers in microbiology 61 30619149
2017 SMARCB1/INI1 Involvement in Pediatric Chordoma: A Mutational and Immunohistochemical Analysis. The American journal of surgical pathology 57 27635948
2018 SWI/SNF Chromatin-remodeling Complex Status in SMARCB1/INI1-preserved Epithelioid Sarcoma. The American journal of surgical pathology 54 29309303
2017 SMARCB1/INI1 Loss in Epithelioid Schwannoma: A Clinicopathologic and Immunohistochemical Study of 65 Cases. The American journal of surgical pathology 51 28368924
2015 Reappraisal of sinonasal undifferentiated carcinoma: SMARCB1 (INI1)-deficient sinonasal carcinoma: a single-institution experience. Virchows Archiv : an international journal of pathology 50 26407663
2019 Desmoplastic myxoid tumor, SMARCB1-mutant: clinical, histopathological and molecular characterization of a pineal region tumor encountered in adolescents and adults. Acta neuropathologica 47 31732806
2012 Expression of SMARCB1 (INI1) mutations in familial schwannomatosis. Human molecular genetics 47 22949514
2024 Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF. Nature 46 38538798
2021 A Role for SMARCB1 in Synovial Sarcomagenesis Reveals That SS18-SSX Induces Canonical BAF Destruction. Cancer discovery 46 34078620
2020 Loss of the SWI/SNF-ATPase subunit members SMARCF1 (ARID1A), SMARCA2 (BRM), SMARCA4 (BRG1) and SMARCB1 (INI1) in oesophageal adenocarcinoma. BMC cancer 45 31906887
2019 Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition. eLife 45 30860482
2002 Chromatin remodeling factor encoded by ini1 induces G1 arrest and apoptosis in ini1-deficient cells. Oncogene 44 12082626
2014 ERG and SALL4 expressions in SMARCB1/INI1-deficient tumors: a useful tool for distinguishing epithelioid sarcoma from malignant rhabdoid tumor. Human pathology 43 25479928
2009 Crucial roles for interactions between MLL3/4 and INI1 in nuclear receptor transactivation. Molecular endocrinology (Baltimore, Md.) 43 19221051
2015 SMARCB1-deficient Vulvar Neoplasms: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 14 Cases. The American journal of surgical pathology 41 25651469
2020 Genomic and Immunologic Characterization of INI1-Deficient Pediatric Cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 40 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 37 23576573
2007 INI1 induces interferon signaling and spindle checkpoint in rhabdoid tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 36 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
2003 The Drosophila SNR1 (SNF5/INI1) subunit directs essential developmental functions of the Brahma chromatin remodeling complex. Molecular and cellular biology 34 12482982
2024 The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer. Nature communications 31 38355560
2014 Concurrent loss of INI1, PBRM1, and BRM expression in epithelioid sarcoma: implications for the cocontributions of multiple SWI/SNF complex members to pathogenesis. Human pathology 30 25200863
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
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
2013 Loss of IGFBP7 expression and persistent AKT activation contribute to SMARCB1/Snf5-mediated tumorigenesis. Oncogene 29 23851500
2020 Tumor-Suppressive Function of lncRNA-MEG3 in Glioma Cells by Regulating miR-6088/SMARCB1 Axis. BioMed research international 28 32420340
2023 SMARCB1 regulates a TFCP2L1-MYC transcriptional switch promoting renal medullary carcinoma transformation and ferroptosis resistance. Nature communications 27 37236926
2023 SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors. Nature communications 27 38040699
2020 Nucleoporin 210 Serves a Key Scaffold for SMARCB1 in Liver Cancer. Cancer research 27 33239431
2003 Molecular heterogeneity of meningioma with INI1 mutation. Molecular pathology : MP 26 14514925
1999 The mouse ortholog of the human SMARCB1 gene encodes two splice forms. Biochemical and biophysical research communications 26 10208879
2020 SMARCB1/INI1-deficient tumors of adulthood. F1000Research 25 33796273
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
2004 SNR1 (INI1/SNF5) mediates important cell growth functions of the Drosophila Brahma (SWI/SNF) chromatin remodeling complex. Genetics 23 15454538
2021 SMARCB1 deletion in atypical teratoid rhabdoid tumors results in human endogenous retrovirus K (HML-2) expression. Scientific reports 22 34145313
2011 Proximal-type epithelioid sarcoma of the vulva with INI1 diagnostic utility. Annals of diagnostic pathology 22 21724432
2006 dDYRK2 and Minibrain interact with the chromatin remodelling factors SNR1 and TRX. The Biochemical journal 22 16671894
2023 SMARCB1 regulates the hypoxic stress response in sickle cell trait. Proceedings of the National Academy of Sciences of the United States of America 21 37186844
2021 Poorly differentiated chordoma showing loss of SMARCB1/INI1: Clinicopathological and radiological spectrum of nine cases, including uncommon features of a relatively under-recognized entity. Annals of diagnostic pathology 20 34482218
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
2013 INI1/hSNF5-interaction defective HIV-1 IN mutants exhibit impaired particle morphology, reverse transcription and integration in vivo. Retrovirology 20 23799881
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 SMARCA4-deficient rhabdoid tumours show intermediate molecular features between SMARCB1-deficient rhabdoid tumours and small cell carcinomas of the ovary, hypercalcaemic type. The Journal of pathology 19 33999421
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 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
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 17 35864317
2016 The SWI/SNF Complex Protein Snr1 Is a Tumor Suppressor in Drosophila Imaginal Tissues. Cancer research 17 27923836