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Gene Review

SMARCA4  -  SWI/SNF related, matrix associated, actin...

Homo sapiens

Synonyms: ATP-dependent helicase SMARCA4, BAF190, BAF190A, BRG1, BRG1-associated factor 190A, ...
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Disease relevance of SMARCA4


High impact information on SMARCA4

  • We show that BRCA1 can directly interact with the BRG1 subunit of the SWI/SNF complex [6].
  • Coimmunoprecipitation experiments suggested BRG1 associates with the RB family in vivo [7].
  • In the human carcinoma cell line SW13, BRG1 exhibited tumor suppressor activity by inducing formation of flat, growth-arrested cells [7].
  • A lysine to arginine substitution at the corresponding residue of BRG1 also generated a transcriptional dominant negative in human cells [8].
  • Loss of Brg1 or HDAC2 should therefore produce Gc resistance, and we show that approximately 50% of Gc-resistant human and dog corticotroph adenomas, which are the hallmark of Cushing disease, are deficient in nuclear expression of either protein [9].

Chemical compound and disease context of SMARCA4

  • We have investigated here the function of SNF2beta-BRG1 in the RA receptor-retinoid X receptor-mediated transduction of the retinoid signal in F9 embryonal carcinoma (EC) cells which differentiate into endodermal-like cells upon RA treatment [10].

Biological context of SMARCA4


Anatomical context of SMARCA4


Associations of SMARCA4 with chemical compounds

  • Inhibition of histone deacetylation by trichostatin A dramatically increases BRG-1-mediated coactivation of ER signaling, and this increase is reversed by overexpression of histone deacetylase 1 [17].
  • BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation [17].
  • Using the yeast two-hybrid system, we now demonstrate that the N-terminal regions of hSNF2alpha and hSNF2beta, preceding the DNA-dependent ATPase domain, specifically interact with the region of the estrogen receptor (ER) which includes the ligand binding domain and the ligand-dependent activation function AF-2 [18].
  • Mutation of lysine residue 798 in the DNA-dependent ATPase domain of BRG1 significantly reduced its ability to repress c-fos transcription [3].
  • The Brg1 subunit of SWI/SNF and the TRAP230 subunit of TRAP/Mediator were shown to interact directly with RTA [19].

Physical interactions of SMARCA4


Co-localisations of SMARCA4


Regulatory relationships of SMARCA4


Other interactions of SMARCA4

  • IFN-gamma induction of the CIITA (class II transactivator) promoter (pIV) requires Brahma-related gene 1 (BRG1), a chromatin-remodeling enzyme [29].
  • Furthermore, BRG1 is required for IFN-induced restriction enzyme and DNase I accessibility at promoters [29].
  • In contrast, constitutive BRG1 association at IFN targets is STAT1-independent [29].
  • Finally, we demonstrate that BRG-1-mediated coactivation of ER signaling is regulated by the state of histone acetylation within a cell [17].
  • In contrast, the amount of ZNF185 transcript clearly varied among lung cancer cell lines and severely reduced levels were observed in BRG1-deficient cells, except those of A427 [11].
  • Taken together, we provided evidence that Brg1 is preferentially recruited by p53 for inducing a subset of target genes through chromatin remodeling [30].

Analytical, diagnostic and therapeutic context of SMARCA4


  1. Genetic and epigenetic screening for gene alterations of the chromatin-remodeling factor, SMARCA4/BRG1, in lung tumors. Medina, P.P., Carretero, J., Fraga, M.F., Esteller, M., Sidransky, D., Sanchez-Cespedes, M. Genes Chromosomes Cancer (2004) [Pubmed]
  2. BRG1 controls the activity of the retinoblastoma protein via regulation of p21CIP1/WAF1/SDI. Kang, H., Cui, K., Zhao, K. Mol. Cell. Biol. (2004) [Pubmed]
  3. Human SWI-SNF component BRG1 represses transcription of the c-fos gene. Murphy, D.J., Hardy, S., Engel, D.A. Mol. Cell. Biol. (1999) [Pubmed]
  4. Reconstitution of glucocorticoid receptor-dependent transcription in vivo. Trotter, K.W., Archer, T.K. Mol. Cell. Biol. (2004) [Pubmed]
  5. Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex. Otsuki, T., Furukawa, Y., Ikeda, K., Endo, H., Yamashita, T., Shinohara, A., Iwamatsu, A., Ozawa, K., Liu, J.M. Hum. Mol. Genet. (2001) [Pubmed]
  6. BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer. Bochar, D.A., Wang, L., Beniya, H., Kinev, A., Xue, Y., Lane, W.S., Wang, W., Kashanchi, F., Shiekhattar, R. Cell (2000) [Pubmed]
  7. The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Dunaief, J.L., Strober, B.E., Guha, S., Khavari, P.A., Alin, K., Luban, J., Begemann, M., Crabtree, G.R., Goff, S.P. Cell (1994) [Pubmed]
  8. BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Khavari, P.A., Peterson, C.L., Tamkun, J.W., Mendel, D.B., Crabtree, G.R. Nature (1993) [Pubmed]
  9. Role of Brg1 and HDAC2 in GR trans-repression of the pituitary POMC gene and misexpression in Cushing disease. Bilodeau, S., Vallette-Kasic, S., Gauthier, Y., Figarella-Branger, D., Brue, T., Berthelet, F., Lacroix, A., Batista, D., Stratakis, C., Hanson, J., Meij, B., Drouin, J. Genes Dev. (2006) [Pubmed]
  10. SNF2beta-BRG1 is essential for the viability of F9 murine embryonal carcinoma cells. Sumi-Ichinose, C., Ichinose, H., Metzger, D., Chambon, P. Mol. Cell. Biol. (1997) [Pubmed]
  11. Transcriptional targets of the chromatin-remodelling factor SMARCA4/BRG1 in lung cancer cells. Medina, P.P., Carretero, J., Ballestar, E., Angulo, B., Lopez-Rios, F., Esteller, M., Sanchez-Cespedes, M. Hum. Mol. Genet. (2005) [Pubmed]
  12. Purification and biochemical heterogeneity of the mammalian SWI-SNF complex. Wang, W., Côté, J., Xue, Y., Zhou, S., Khavari, P.A., Biggar, S.R., Muchardt, C., Kalpana, G.V., Goff, S.P., Yaniv, M., Workman, J.L., Crabtree, G.R. EMBO J. (1996) [Pubmed]
  13. REST repression of neuronal genes requires components of the hSWI.SNF complex. Battaglioli, E., Andrés, M.E., Rose, D.W., Chenoweth, J.G., Rosenfeld, M.G., Anderson, M.E., Mandel, G. J. Biol. Chem. (2002) [Pubmed]
  14. Selective interaction between the chromatin-remodeling factor BRG1 and the heterochromatin-associated protein HP1alpha. Nielsen, A.L., Sanchez, C., Ichinose, H., Cerviño, M., Lerouge, T., Chambon, P., Losson, R. EMBO J. (2002) [Pubmed]
  15. LIM-only protein, CRP2, switched on smooth muscle gene activity in adult cardiac myocytes. Chang, D.F., Belaguli, N.S., Chang, J., Schwartz, R.J. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  16. BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines. Wong, A.K., Shanahan, F., Chen, Y., Lian, L., Ha, P., Hendricks, K., Ghaffari, S., Iliev, D., Penn, B., Woodland, A.M., Smith, R., Salada, G., Carillo, A., Laity, K., Gupte, J., Swedlund, B., Tavtigian, S.V., Teng, D.H., Lees, E. Cancer Res. (2000) [Pubmed]
  17. BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation. DiRenzo, J., Shang, Y., Phelan, M., Sif, S., Myers, M., Kingston, R., Brown, M. Mol. Cell. Biol. (2000) [Pubmed]
  18. Ligand-dependent interaction between the estrogen receptor and the human homologues of SWI2/SNF2. Ichinose, H., Garnier, J.M., Chambon, P., Losson, R. Gene (1997) [Pubmed]
  19. Principal role of TRAP/mediator and SWI/SNF complexes in Kaposi's sarcoma-associated herpesvirus RTA-mediated lytic reactivation. Gwack, Y., Baek, H.J., Nakamura, H., Lee, S.H., Meisterernst, M., Roeder, R.G., Jung, J.U. Mol. Cell. Biol. (2003) [Pubmed]
  20. BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation. Hsiao, P.W., Fryer, C.J., Trotter, K.W., Wang, W., Archer, T.K. Mol. Cell. Biol. (2003) [Pubmed]
  21. EVI1 promotes cell proliferation by interacting with BRG1 and blocking the repression of BRG1 on E2F1 activity. Chi, Y., Senyuk, V., Chakraborty, S., Nucifora, G. J. Biol. Chem. (2003) [Pubmed]
  22. LKB1 associates with Brg1 and is necessary for Brg1-induced growth arrest. Marignani, P.A., Kanai, F., Carpenter, C.L. J. Biol. Chem. (2001) [Pubmed]
  23. Chromatin-remodelling factor BRG1 selectively activates a subset of interferon-alpha-inducible genes. Huang, M., Qian, F., Hu, Y., Ang, C., Li, Z., Wen, Z. Nat. Cell Biol. (2002) [Pubmed]
  24. Multiple interactions between BRG1 and MHC class II promoter binding proteins. Mudhasani, R., Fontes, J.D. Mol. Immunol. (2005) [Pubmed]
  25. BAF complex is closely related to and interacts with NF1/CTF and RNA polymerase II in gene transcriptional activation. Zhao, L.H., Ba, X.Q., Wang, X.G., Zhu, X.J., Wang, L., Zeng, X.L. Acta Biochim. Biophys. Sin. (Shanghai) (2005) [Pubmed]
  26. Interferon-gamma-induced chromatin remodeling at the CIITA locus is BRG1 dependent. Pattenden, S.G., Klose, R., Karaskov, E., Bremner, R. EMBO J. (2002) [Pubmed]
  27. SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription. Lee, D., Kim, J.W., Seo, T., Hwang, S.G., Choi, E.J., Choe, J. J. Biol. Chem. (2002) [Pubmed]
  28. Implication of BRG1 and cdk9 in the STAT3-mediated activation of the p21waf1 gene. Giraud, S., Hurlstone, A., Avril, S., Coqueret, O. Oncogene (2004) [Pubmed]
  29. Apical role for BRG1 in cytokine-induced promoter assembly. Ni, Z., Karaskov, E., Yu, T., Callaghan, S.M., Der, S., Park, D.S., Xu, Z., Pattenden, S.G., Bremner, R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  30. The activity of p53 is differentially regulated by Brm- and Brg1-containing SWI/SNF chromatin remodeling complexes. Xu, Y., Zhang, J., Chen, X. J. Biol. Chem. (2007) [Pubmed]
  31. Role for BRG1 in cell cycle control and tumor suppression. Hendricks, K.B., Shanahan, F., Lees, E. Mol. Cell. Biol. (2004) [Pubmed]
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