Gene Symbol: Smarca4
Description: SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4
Alias: brg-1, transcription activator BRG1, ATP-dependent helicase SMARCA4, BAF190A, BRG1-associated factor 190A, SNF2-beta, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4, protein brahma homolog 1
Species: rat
Products:     Smarca4

Top Publications

  1. Indra A, Dupé V, Bornert J, Messaddeq N, Yaniv M, Mark M, et al. Temporally controlled targeted somatic mutagenesis in embryonic surface ectoderm and fetal epidermal keratinocytes unveils two distinct developmental functions of BRG1 in limb morphogenesis and skin barrier formation. Development. 2005;132:4533-44 pubmed
    ..Finally, we demonstrate that cell-specific targeted somatic mutations can be created at various times during the development of mouse embryos cell-specifically expressing the tamoxifen-activatable Cre-ER(T2) recombinase. ..
  2. Legouy E, Thompson E, Muchardt C, Renard J. Differential preimplantation regulation of two mouse homologues of the yeast SWI2 protein. Dev Dyn. 1998;212:38-48 pubmed
    ..These results indicate that the two murine homologues of SWI2 have substantially different roles in chromatin organization during the onset of embryonic development. ..
  3. Khavari P, Peterson C, Tamkun J, Mendel D, Crabtree G. BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature. 1993;366:170-4 pubmed
    ..These results show that the SWI2 family DNA-dependent ATPase domain has functional conservation between yeast and humans and suggest that a SWI/SNF protein complex is required for the activation of selective mammalian genes. ..
  4. Remboutsika E, Lutz Y, Gansmuller A, Vonesch J, Losson R, Chambon P. The putative nuclear receptor mediator TIF1alpha is tightly associated with euchromatin. J Cell Sci. 1999;112 ( Pt 11):1671-83 pubmed
    ..g. liganded nuclear receptors) to their cognate sites in target genes, thereby participitating in the epigenetic control of transcription during embryonic development and cell differentiation. ..
  5. Medina P, Carretero J, Fraga M, Esteller M, Sidransky D, Sanchez Cespedes M. Genetic and epigenetic screening for gene alterations of the chromatin-remodeling factor, SMARCA4/BRG1, in lung tumors. Genes Chromosomes Cancer. 2004;41:170-7 pubmed
    The SMARCA4/BRG1 gene product is a component of the SWI-SNF chromatin-remodeling complex and regulates gene expression by disrupting histone-DNA contacts in an ATP-dependent manner...
  6. Gebuhr T, Kovalev G, Bultman S, Godfrey V, Su L, Magnuson T. The role of Brg1, a catalytic subunit of mammalian chromatin-remodeling complexes, in T cell development. J Exp Med. 2003;198:1937-49 pubmed
    ..These results highlight the importance of chromatin-remodeling complexes at different stages in the development of a mammalian cell lineage. ..
  7. Zhou J, Zhang M, Fang H, El Mounayri O, Rodenberg J, Imbalzano A, et al. The SWI/SNF chromatin remodeling complex regulates myocardin-induced smooth muscle-specific gene expression. Arterioscler Thromb Vasc Biol. 2009;29:921-8 pubmed publisher
    ..These data demonstrate that the ability of myocardin to induce smooth muscle-specific gene expression is dependent on its interaction with SWI/SNF ATP-dependent chromatin remodeling complexes. ..
  8. Park J, Venteicher A, Hong J, Choi J, Jun S, Shkreli M, et al. Telomerase modulates Wnt signalling by association with target gene chromatin. Nature. 2009;460:66-72 pubmed publisher
    ..The telomerase protein component TERT (telomerase reverse transcriptase) interacts with BRG1 (also called SMARCA4), a SWI/SNF-related chromatin remodelling protein, and activates Wnt-dependent reporters in cultured cells and in ..
  9. Bultman S, Gebuhr T, Yee D, La Mantia C, Nicholson J, Gilliam A, et al. A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Mol Cell. 2000;6:1287-95 pubmed
    ..In addition, Brg1 heterozygotes are predisposed to exencephaly and tumors. These results provide evidence that biochemically similar chromatin-remodeling complexes have dramatically different functions during mammalian development...

More Information


  1. Xu Y, Zhang J, Chen X. The activity of p53 is differentially regulated by Brm- and Brg1-containing SWI/SNF chromatin remodeling complexes. J Biol Chem. 2007;282:37429-35 pubmed
    ..Thus, we hypothesize that the potential tumor suppressor function for Brg1 is mediated in part through the p53 pathway. ..
  2. Jenkins B, Pullen C, Darimont B. Novel glucocorticoid receptor coactivator effector mechanisms. Trends Endocrinol Metab. 2001;12:122-6 pubmed
    ..The emerging picture shows coactivators as flexible, but precise, coordinators of complex and dynamic networks, in which transcriptional regulation by GR and other NRs is linked to other signaling pathways. ..
  3. Mehta G, Kumarasamy S, Wu J, Walsh A, Liu L, WILLIAMS K, et al. MITF interacts with the SWI/SNF subunit, BRG1, to promote GATA4 expression in cardiac hypertrophy. J Mol Cell Cardiol. 2015;88:101-10 pubmed publisher
    ..Thus, in hypertrophic cardiomyoctes, MITF is a key transcriptional activator of a pro-hypertrophic gene, GATA4, and this regulation is dependent upon the BRG1 component of the SWI/SNF complex. ..
  4. Lee D, Kim J, Seo T, Hwang S, Choi E, Choe J. SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription. J Biol Chem. 2002;277:22330-7 pubmed
  5. Xu J, Lei S, Liu Y, Gao X, Irwin M, Xia Z, et al. Antioxidant N-acetylcysteine attenuates the reduction of Brg1 protein expression in the myocardium of type 1 diabetic rats. J Diabetes Res. 2013;2013:716219 pubmed publisher
    ..In conclusion, myocardial Brg1 is reduced in diabetes and enhancement of cardiac Brg1 expression may represent a novel mechanism whereby NAC confers cardioprotection. ..
  6. Lassmann T, Maida Y, Tomaru Y, Yasukawa M, Ando Y, Kojima M, et al. Telomerase reverse transcriptase regulates microRNAs. Int J Mol Sci. 2015;16:1192-208 pubmed publisher
    ..Similar results were obtained with the suppression of either BRG1 (also called SMARCA4) or nucleostemin, which are proteins interacting with TERT and functioning beyond telomeres...
  7. Chiba H, Muramatsu M, Nomoto A, Kato H. Two human homologues of Saccharomyces cerevisiae SWI2/SNF2 and Drosophila brahma are transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor. Nucleic Acids Res. 1994;22:1815-20 pubmed
    ..No enhancement was observed for promoters which do not respond to nuclear receptors. We suggest that global transcriptional coactivators equivalent to the yeast SWI/SNF complex exist in mammalian cells. ..
  8. Datta J, Majumder S, Bai S, Ghoshal K, Kutay H, Smith D, et al. Physical and functional interaction of DNA methyltransferase 3A with Mbd3 and Brg1 in mouse lymphosarcoma cells. Cancer Res. 2005;65:10891-900 pubmed
    ..Coexpression of two of the three interacting proteins at a time augmented their repressor function. This study shows physical and functional interaction of Dnmt3a with components of nucleosome remodeling machinery. ..
  9. Torres Padilla M, Zernicka Goetz M. Role of TIF1alpha as a modulator of embryonic transcription in the mouse zygote. J Cell Biol. 2006;174:329-38 pubmed
    ..These studies indicate that TIF1alpha is a factor that modulates the expression of a set of genes during the first wave of genome activation in the mouse embryo. ..
  10. Ostlund Farrants A, Blomquist P, Kwon H, Wrange O. Glucocorticoid receptor-glucocorticoid response element binding stimulates nucleosome disruption by the SWI/SNF complex. Mol Cell Biol. 1997;17:895-905 pubmed
    ..No such effect was seen on binding of GR to its response element. Our results suggest that GR, but not NF1, is able to target the nucleosome-disrupting activity of the SWI/SNF complex. ..
  11. Wang S, Zhang B, Faller D. Prohibitin requires Brg-1 and Brm for the repression of E2F and cell growth. EMBO J. 2002;21:3019-28 pubmed
  12. Battaglioli E, Andrés M, Rose D, Chenoweth J, Rosenfeld M, Anderson M, et al. REST repression of neuronal genes requires components of the hSWI.SNF complex. J Biol Chem. 2002;277:41038-45 pubmed
    ..Together, our data suggest that ATP-dependent chromatin remodeling, as well as histone deacetylation, is needed for REST-mediated repression. ..
  13. Cui H, Schlesinger J, Schoenhals S, Tönjes M, Dunkel I, Meierhofer D, et al. Phosphorylation of the chromatin remodeling factor DPF3a induces cardiac hypertrophy through releasing HEY repressors from DNA. Nucleic Acids Res. 2016;44:2538-53 pubmed publisher
    ..Thus, we present a novel pathway for pathological cardiac hypertrophy, whose inhibition is a long-term therapeutic goal for the treatment of the course of heart failure. ..
  14. Hsiao P, Fryer C, Trotter K, Wang W, Archer T. BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation. Mol Cell Biol. 2003;23:6210-20 pubmed
    ..Thus, in addition to previously identified BAF250, BAF60a may provide another critical and direct link between nuclear receptors and the BRG1 complex that is required for promoter recruitment and subsequent chromatin remodeling. ..
  15. Lamba D, Hayes S, Karl M, Reh T. Baf60c is a component of the neural progenitor-specific BAF complex in developing retina. Dev Dyn. 2008;237:3016-23 pubmed publisher
    ..Finally, we show that Baf60c is re-expressed in the Müller glial cells that re-enter the cell cycle after neurotoxic damage. ..
  16. Yu Y, Chen Y, Kim B, Wang H, Zhao C, He X, et al. Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation. Cell. 2013;152:248-61 pubmed publisher
    ..Here, we demonstrate that activation of ATP-dependent SWI/SNF chromatin-remodeling enzyme Smarca4/Brg1 at the differentiation onset is necessary and sufficient to initiate and promote oligodendrocyte lineage ..
  17. Ke X, McKnight R, Gracey Maniar L, Sun Y, Callaway C, Majnik A, et al. IUGR increases chromatin-remodeling factor Brg1 expression and binding to GR exon 1.7 promoter in newborn male rat hippocampus. Am J Physiol Regul Integr Comp Physiol. 2015;309:R119-27 pubmed publisher
    ..7 was located within a nucleosome-depleted region. We speculate that changes in hippocampal Brg1 expression mediate GR expression and subsequently trigger neuroendocrine reprogramming in male IUGR rats. ..
  18. Qiu Z, Ghosh A. A calcium-dependent switch in a CREST-BRG1 complex regulates activity-dependent gene expression. Neuron. 2008;60:775-87 pubmed publisher
  19. Sanchez R, Meslamani J, Zhou M. The bromodomain: from epigenome reader to druggable target. Biochim Biophys Acta. 2014;1839:676-85 pubmed publisher
    ..This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function. ..
  20. Li W, Xiong Y, Shang C, Twu K, Hang C, Yang J, et al. Brg1 governs distinct pathways to direct multiple aspects of mammalian neural crest cell development. Proc Natl Acad Sci U S A. 2013;110:1738-43 pubmed publisher
    ..Our findings reveal an important role for Brg1 and its downstream pathways in the survival, differentiation, and migration of the multipotent NCCs critical for mammalian cardiovascular development. ..
  21. Qi H, Wang Y, Zhang Q, Guo J, Li L, Cao Y, et al. Activation of peroxisome proliferator-activated receptor γ (PPARγ) through NF-κB/Brg1 and TGF-β1 pathways attenuates cardiac remodeling in pressure-overloaded rat hearts. Cell Physiol Biochem. 2015;35:899-912 pubmed publisher
  22. Ahmed M, Xu J, Xu P. EYA1 and SIX1 drive the neuronal developmental program in cooperation with the SWI/SNF chromatin-remodeling complex and SOX2 in the mammalian inner ear. Development. 2012;139:1965-77 pubmed publisher
  23. Napolitano M, Cipollaro M, Cascino A, Melone M, Giordano A, Galderisi U. Brg1 chromatin remodeling factor is involved in cell growth arrest, apoptosis and senescence of rat mesenchymal stem cells. J Cell Sci. 2007;120:2904-11 pubmed
    ..To this end, in MSCs we caused a forced expression of the ATPase subunit of SWI/SNF (Brg1 - also known as Smarca4) by adenoviral transduction. Forced Brg1 expression induced a significant cell cycle arrest of MSCs in culture...
  24. Singh M, Popowicz G, Krajewski M, Holak T. Structural ramification for acetyl-lysine recognition by the bromodomain of human BRG1 protein, a central ATPase of the SWI/SNF remodeling complex. Chembiochem. 2007;8:1308-16 pubmed
    ..By modeling the acetylated-lysine peptide into the BRG1 bromodomain structure, we were able to explain the weak binding of acetylated-lysine peptides to this bromodomain. ..
  25. Kadoch C, Crabtree G. Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell. 2013;153:71-85 pubmed publisher
    ..This mechanism of transformation depends on only two amino acids of SSX, providing a potential foundation for therapeutic intervention. ..
  26. Mahmoudi T, Parra M, Vries R, Kauder S, Verrijzer C, Ott M, et al. The SWI/SNF chromatin-remodeling complex is a cofactor for Tat transactivation of the HIV promoter. J Biol Chem. 2006;281:19960-8 pubmed
    ..This synergism depended on the acetyltransferase activity of p300 and on Tat Lys(50) and Lys(51). In conclusion, Tat-mediated activation of the HIV promoter requires the SWI/SNF complex in synergy with the coactivator p300. ..
  27. Xue Y, Canman J, Lee C, Nie Z, Yang D, Moreno G, et al. The human SWI/SNF-B chromatin-remodeling complex is related to yeast rsc and localizes at kinetochores of mitotic chromosomes. Proc Natl Acad Sci U S A. 2000;97:13015-20 pubmed
    ..Our data suggest that SWI/SNF-B and Rsc represent a novel subfamily of chromatin-remodeling complexes conserved from yeast to human, and could participate in cell division at kinetochores of mitotic chromosomes. ..
  28. Valdman A, Nordenskjold A, Fang X, Naito A, Al Shukri S, Larsson C, et al. Mutation analysis of the BRG1 gene in prostate cancer clinical samples. Int J Oncol. 2003;22:1003-7 pubmed
    ..In conclusion, the study excludes the presence of common BRG1 mutations in prostate cancer. ..
  29. Kidder B, Palmer S. Examination of transcriptional networks reveals an important role for TCFAP2C, SMARCA4, and EOMES in trophoblast stem cell maintenance. Genome Res. 2010;20:458-72 pubmed publisher
    ..analysis to investigate targets of the TFs-TCFAP2C, EOMES, ETS2, and GATA3-and a chromatin remodeling factor, SMARCA4. We then evaluated the transcriptional states of target genes using transcriptome analysis and genome-wide ..
  30. Wang Z, Martin J, Mueller L, Caccamise A, Werner C, Neve R, et al. BRG1 in the Nucleus Accumbens Regulates Cocaine-Seeking Behavior. Biol Psychiatry. 2016;80:652-660 pubmed publisher
    ..Here, we examined the possible interaction of BRG1-also known as SMARCA4, an adenosine triphosphatase-containing chromatin remodeler-and SMAD3 in response to cocaine exposure...
  31. Dhar S, Thota A, Rao M. Insights into role of bromodomain, testis-specific (Brdt) in acetylated histone H4-dependent chromatin remodeling in mammalian spermiogenesis. J Biol Chem. 2012;287:6387-405 pubmed publisher
    ..Thus, our results indicate this interaction to be a vital step in the chromatin remodeling process during mammalian spermiogenesis. ..
  32. Sánchez Tilló E, Lazaro A, Torrent R, Cuatrecasas M, Vaquero E, Castells A, et al. ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. Oncogene. 2010;29:3490-500 pubmed publisher
    ..Our results identify ZEB1/BRG1 as a new transcriptional mechanism regulating E-cadherin expression and epithelial-to-mesenchymal transdifferentiation that may be involved during the initial stages of tumor invasion. ..
  33. Sun A, Tawfik O, Gayed B, Thrasher J, Hoestje S, Li C, et al. Aberrant expression of SWI/SNF catalytic subunits BRG1/BRM is associated with tumor development and increased invasiveness in prostate cancers. Prostate. 2007;67:203-13 pubmed
    ..We provide the first evidence that aberrant expression of BRG1 and BRM genes is associated with disease development and progression in prostate cancers and increased BRG1 expression may promote tumor growth and invasion. ..
  34. Vizlin Hodzic D, Runnberg R, Ryme J, Simonsson S, Simonsson T. SAF-A forms a complex with BRG1 and both components are required for RNA polymerase II mediated transcription. PLoS ONE. 2011;6:e28049 pubmed publisher
    ..We demonstrate that SAF-A interacts with BRG1 and that both components are required for RNA Polymerase II Mediated Transcription. ..
  35. Dai Y, Ngo D, Jacob J, Forman L, Faller D. Prohibitin and the SWI/SNF ATPase subunit BRG1 are required for effective androgen antagonist-mediated transcriptional repression of androgen receptor-regulated genes. Carcinogenesis. 2008;29:1725-33 pubmed publisher
    ..Furthermore, in addition to its necessary role in AR-mediated transcriptional repression, we demonstrate that prohibitin is required for full and efficient androgen antagonist-mediated growth suppression of prostate cancer cells. ..
  36. Lee Y, Sohn D, Han D, Lee H, Seong R, Kim J. Chromatin remodeling complex interacts with ADD1/SREBP1c to mediate insulin-dependent regulation of gene expression. Mol Cell Biol. 2007;27:438-52 pubmed
    ..Taken together, our results suggest that the SWI/SNF chromatin remodeling complexes confer not only insulin-dependent gene expression but also insulin sensitivity in vivo via interaction with ADD1/SREBP1c. ..
  37. Young D, Pratap J, Javed A, Weiner B, Ohkawa Y, van Wijnen A, et al. SWI/SNF chromatin remodeling complex is obligatory for BMP2-induced, Runx2-dependent skeletal gene expression that controls osteoblast differentiation. J Cell Biochem. 2005;94:720-30 pubmed
    ..Taken together these results support the concept that BMP2-mediated osteogenesis requires Runx2, and demonstrates that initiation of BMP2-induced, Runx2-dependent skeletal gene expression requires SWI/SNF chromatin remodeling complexes. ..
  38. Costa Y, Speed R, Gautier P, Semple C, Maratou K, Turner J, et al. Mouse MAELSTROM: the link between meiotic silencing of unsynapsed chromatin and microRNA pathway?. Hum Mol Genet. 2006;15:2324-34 pubmed
    ..The presence of MAEL in these critical compartments of male germ cells and its interactions provide a link suggesting the involvement of the miRNA pathway in MSUC...
  39. Huuskonen J, Vishnu M, Fielding P, Fielding C. Activation of ATP-binding cassette transporter A1 transcription by chromatin remodeling complex. Arterioscler Thromb Vasc Biol. 2005;25:1180-5 pubmed
    ..In this study, we investigated the activation of ABCA1 by brahma-related gene 1 (BRG-1) and brahma, members of the SWI/SNF (mating type switching/sucrose nonfermenting) chromatin remodeling complex...
  40. Giacinti C, Bagella L, Puri P, Giordano A, Simone C. MyoD recruits the cdk9/cyclin T2 complex on myogenic-genes regulatory regions. J Cell Physiol. 2006;206:807-13 pubmed
  41. He S, Pirity M, Wang W, Wolf L, Chauhan B, Cveklova K, et al. Chromatin remodeling enzyme Brg1 is required for mouse lens fiber cell terminal differentiation and its denucleation. Epigenetics Chromatin. 2010;3:21 pubmed publisher
    Brahma-related gene 1 (Brg1, also known as Smarca4 and Snf2?) encodes an adenosine-5'-triphosphate (ATP)-dependent catalytical subunit of the (switch/sucrose nonfermentable) (SWI/SNF) chromatin remodeling complexes...
  42. Wang W, Cote J, Xue Y, Zhou S, Khavari P, Biggar S, et al. Purification and biochemical heterogeneity of the mammalian SWI-SNF complex. EMBO J. 1996;15:5370-82 pubmed
    ..Certain cell lines completely lack BRG1 and hbrm, indicating that they are not essential for cell viability and that the mammalian SWI-SNF complex may be tailored to the needs of a differentiated cell type. ..
  43. Bochar D, Wang L, Beniya H, Kinev A, Xue Y, Lane W, et al. BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer. Cell. 2000;102:257-65 pubmed
    ..These findings reveal a direct function for BRCA1 in transcriptional control through modulation of chromatin structure. ..
  44. Mehrotra A, Joe B, de la Serna I. SWI/SNF chromatin remodeling enzymes are associated with cardiac hypertrophy in a genetic rat model of hypertension. J Cell Physiol. 2013;228:2337-42 pubmed publisher
    ..Thus we provide novel insights into the epigenetic mechanisms by which salt induced hypertension leads to cardiac hypertrophy. ..
  45. Inayoshi Y, Miyake K, Machida Y, Kaneoka H, Terajima M, Dohda T, et al. Mammalian chromatin remodeling complex SWI/SNF is essential for enhanced expression of the albumin gene during liver development. J Biochem. 2006;139:177-88 pubmed
    ..Our findings suggest that the mechanism by which the activity of transcription factors is enhanced by RB family members and SWI/SNF includes an increase in the ATPase activity of the chromatin remodeling complex. ..
  46. Rotival M, Ko J, Srivastava P, Kerloc h A, Montoya A, Mauro C, et al. Integrating phosphoproteome and transcriptome reveals new determinants of macrophage multinucleation. Mol Cell Proteomics. 2015;14:484-98 pubmed publisher link differential phosphorylation with the transcriptomic reprogramming of macrophages and identify LRRFIP1, SMARCA4, and DNMT1 as novel regulators of MM...
  47. Gordon M, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem. 2006;281:22429-33 pubmed
  48. Shain A, Pollack J. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLoS ONE. 2013;8:e55119 pubmed publisher
    ..Mutations occurred most commonly in the SMARCA4 enzymatic subunit, and in subunits thought to confer functional specificity (ARID1A, ARID1B, PBRM1, and ARID2)...