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Symbol SMARCA4 contributors: mct/shn - updated : 22-04-2017
HGNC name SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4
HGNC id 11100
  • N terminus mediating critical protein interactions within SWI/SNF
  • four domains highly related to those found in BRM : a proline-rich domain, six sequence motifs characteristic of DNA dependent ATPases
  • HSA domain of BRG1 is required to mediate the interaction with ARID1A
  • a SNF2 domain
  • a bromodomain
    interspecies homolog to Drosophila ISWI (imitation of SWI)
    homolog to yeast S.cerevisiae SWI/SNF general transcriptional activator
    ortholog to Smarca4, mus musculus
    ortholog to Smarca4, Rattus norvegicus
    ortholog to smarca4, Danio rerio
    ortholog to SMARCA4, Pan troglodytes
  • SNF2/Rad54 helicase family
  • CATEGORY regulatory , DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
  • exclusively nuclear
  • co-localizes with origin recognition complexes, GINS complexes, and proliferating cell nuclear antigen at sites of DNA replication on extended chromatin fibers
  • basic FUNCTION
  • actin-dependent regulator of chromatin structure, generating and interconverting multiple nucleosomes states
  • regulating the expression of CDKN1A and activating RB1 by inducing its hypophosphorylation through up-regulation of the CDKN1A
  • during mitosis, phosphorylated and excluded from the condensed chromosomes
  • controlling cellular proliferation and senescence by modulating the RB1 pathway via multiple mechanisms
  • inducing Z-DNA formation and promoting a transition from a transient and partial remodeling to a more extensive disruption of the canonical nucleosomal structure
  • facilitates REST repression by increasing the interaction between REST and chromatin
  • may be required for embryonic stem cells growth perhaps through functions in addition to transcriptional regulation
  • role in the regulation of thymocyte cell proliferation and survival
  • critical function of Brg-1 in regulating the recruitment of Sp1, Sp3, AP-2, and polymerase II to the MMP-2 promoter
  • plays significant roles in enhancing LXR/RXR-mediated transcription of ABCA1 via the promoter DR-4 element
  • has an apical role in cytokine-induced promoter assembly, acting upstream of STAT complexes at multiple IFN target loci
  • equired for Zygotic genome activation in mammals
  • play a critical role in regulating expression of SRF/MRTFA-dependent smooth muscle-specific genes
  • central ATPase of the SWI/SNF complex, and a critical factor for the functional activity of nuclear receptor complexes
  • enhancing the transcriptional activation by ligand-bound thyroid hormone receptors in a dose-dependent manner
  • playing an essential role in the genesis of specific chromatin loops expanding the repertoire of their functions
  • antagonistic roles for SMARCA2 and SMARCA4 SWI/SNF complexes in differentiation
  • tumor suppressor and a major factor in lung tumorigenesis
  • required in embryonic stem cell maintenance and in blastocysts
  • cooperating with CBP to constrain TP53 activity and permit cancer cell proliferation
  • interprets differentiation signals and plays a causal role in gene regulation, chromatin structure, and cell fate
  • important role for TFAP2C, SMARCA4, and EOMES in trophoblast stem cell self-renewal
  • required for the regulation E-cadherin and the induction of EMT by ZEB1
  • acts as a corepressor of ZEB1 to regulate E-cadherin transcription
  • has a critical role in regulating cardiac growth, differentiation and gene expression
  • required during embryogenesis and has a role as a tumor suppressor to maintain genome stability and prevent cancer
  • plays a direct role in maintenance of genomic stability and with SWI/SNF-related complexes are involved in both double-strand break repair and nucleotide excision repair
  • can escorts POLR2A during elongation and is stabilized at regions with a high density of positioned nucleosomes
  • specifically required to increase transcription of templates with positioned nucleosomes
  • SMARCA2/SMARCA4A switch is an indicator of the responsiveness of a gene to heat-shock or IFNG stimulation and may represent an "on-off switch" of gene expression
  • impacts the canonical Wnt pathway at two different levels in vascular endothelium: through transcriptional regulation of both Wnt receptor genes and Wnt target genes
  • similarly coregulates transcription of a subset of Wnt target genes in vascular endothelial cells
  • interprets both differentiation and activation signals and plays a causal role in gene regulation, chromatin structure, and cell fate
  • SMARCA2 and SMARCA4 play critical roles in regulating development of smooth muscle and SMARCA4 has specific functions within vascular and gastrointestinal smooth muscle that cannot be performed by SMARCA2
  • SMARCA4-mediated chromatin remodeling was crucial for IRF1 access to TRIM22 promoter, thus leading to the transcription of TRIM22 gene
  • SMARCA4 and CHD4 antagonistically modulate Wnt signaling in developing yolk sac vessels to mediate normal vascular remodeling
  • role of SMARCA4/SMARCE1-containing chromatin remodeling complexes in thyroid hormone receptors-regulated gene expression during postembryonic development
  • plays a crucial role in IFNG-induced TRIM22 expression
  • may help IRF1 to overcome the chromatin barrier to activate TRIM22 transcription
  • MBD3 and SMARCA4 antagonistically regulate a common set of genes by regulating promoter nucleosome occupancy
  • role for the mammalian SWI/SNF complex in programmed recombination and repair events that take place during meiosis
  • is required in neural crest cells (NCCs) to direct cardiovascular development
  • important role for SMARCA4 and its downstream pathways in the survival, differentiation, and migration of the multipotent NCCs critical for mammalian cardiovascular development
  • MED14 cooperates with SMARCA4 in the differentiation of skeletogenic neural crest
  • SMARCA4 and SMARCA5 are catalytic subunits of distinct ATP-dependent chromatin remodeling complexes implicated in transcriptional regulation
  • CELLULAR PROCESS cell cycle, division, mitosis
    nucleotide, chromatin organization, remodeling
    nucleotide, transcription
    text RB1-mediated cell cycle arrest
    a component
  • complexing with PB1 (PBAF complex)
  • ZEB1/SMARCA4 as a new transcriptional mechanism in the repression of E-cadherin during epithelial-mesenchymal transition and tumor progression
  • p53-dependent promoter
  • binding positively correlated with gene activity at protein-coding and microRNA (miRNA) genes
  • small molecule nucleotide,
  • ATP
  • protein
  • retinoblastoma protein, RB
  • estrogen receptor, ER
  • Cyclin E
  • beta-actin and BAF53
  • estrogen receptor, ER
  • EKLF
  • mSin3A
  • LKB1
  • Fanconi anemia protein, FANCA
  • hELD/OSA1
  • TMF/ARA160
  • class II transactivator, CIITA
  • REST.CoREST repressor complex
  • signal transducer and activator of transcription 2, STAT2
  • BAF53b
  • heterochromatin-associated protein HP1alpha
  • glucocorticoid receptor, GR
  • Mi-2 beta and RET finger protein
  • PRMT5
  • CARM1
  • STAT3
  • Sp1
  • class II transactivator, CIITA and RFXAP
  • MyoD
  • human zinc finger-containing, Miz1, PIAS-like protein on chromosome 7, hZimp7
  • DNA methyltransferase 3A
  • Heat shock transcription factor (Hsf)-4b
  • Nrf2
  • SRF, and MRTFA
  • activity-dependent neuroprotective protein, ADNP
  • Smad2 and Smad3
  • CDKN2A
  • myocardin
  • Cdx2
  • TERT
  • ARID1A
  • androgen receptor, AR
  • heterochromatin-enriched HP1
  • ZEB1
  • RUNX1
  • HDACs and PARP1
  • is required for MBD3 localization
  • SMARCA4, SMARCB1, and SMARCD1, but not SMARCC1, are the substrates of CHFR for ubiquitination
  • CDK19
  • is essential for PlexinA2 activation and neural crest cells (NCCs) migration
  • functions as a prepatterning factor to direct SMARCA4 to oligodendrocyte-specific enhancers
  • cooperates with CHD7 to activate PlexinA2
  • is an integral component of the transcriptional control of myelination via interaction with OLIG2 at the onset of oligodendrocyte progenitor cells differentiation
  • nuclear-localized SRGAP3 interacts with the SWI/SNF remodeling factor sMARCA4
  • IFNG1 responsiveness of CIITA requires SMARCA4, the ATPase engine of the chromatin remodeling SWI/SNF complex (also called BAF)
  • represses WNT/CTNNB signaling in the nucleus at the level of CTNNB through a SMARCA4-dependent mechanism
  • SMARCA4 and SMARCAL1, both members of the ATP-dependent chromatin remodeling protein family, regulate each other (SMARCA4 binds to the SMARCAL1 promoter, while SMARCAL1 binds to the brg1 promoter)
  • is required for AHR-mediated transcription in ARPE-19 cells
  • SMARCA4 and STAT3 coordinately regulate gene clustering and up-regulate GFAP and OSMR transcription
  • cell & other
    Other stimulates RB activit
    stimulates MYOD-mediated muscle differentiation
    corresponding disease(s) CSSSCA4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    homozygously deleted in prostate and lung carcinomas
    tumoral germinal mutation     loss of function
    inactivating mutations in no-small-cell-lung cancer
    tumoral somatic mutation     loss of function
    in rhabdoid tumors (RTPS2),
    constitutional       gain of function
    in certain patients with hypertrophic cardiomyopathy, its level correlating with disease severity and myosin heavy chain changes
    Variant & Polymorphism
    Candidate gene
    Therapy target
    BRG1/BAF may be a target for treating cardiac hypertrophy and failure
  • Brg1 -/- mice died during the periimplantation stage
  • Brg1 heterozygotes for null mutation are predisposed to exencephaly and tumors
  • T lymphocyte-specific Brg1-deficient mice showed profound thymic abnormalities, CD4 derepression at the double negative (DN; CD4- CD8-) stage, and a developmental block at the DN to double positive (CD4+ CD8+) transition
  • BRG1-depleted oocytes completed meiosis and were fertilized but embryos conceived from BRG1-depleted eggs exhibited a zygotic genome activation phenotype including two-cell arrest and reduced transcription for approximately 30% of expressed genes involved in transcription, RNA processing, and cell cycle regulation
  • Brg1 mutant mouse embryos and RNAi knockdown cells exhibit a 50% reduction in replication fork progression rates, which is associated with decreased cell proliferation
  • genetic ablation of Brg1 in murine embryonic gonocytes results in arrest during prophase of meiosis I
  • mice deficient in the expression of Brg1, a subunit of
  • the complex with ATPase activity, showed defects in early B cell development