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Gene Review

Smarca4  -  SWI/SNF related, matrix associated, actin...

Mus musculus

Synonyms: ATP-dependent helicase SMARCA4, BAF190A, BRG1-associated factor 190A, Baf190a, Brg1, ...
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Disease relevance of Smarca4


High impact information on Smarca4


Biological context of Smarca4

  • Mammalian SWI/SNF complexes utilize either brahma (Brm) or brahma-related gene 1 (Brg1) catalytic subunits to remodel nucleosomes in an ATP-dependent manner [4].
  • However, experiments with other cell types demonstrate that Brg1 is not a general cell survival factor [4].
  • To test this hypothesis, we have generated a Brg1 null mutation by gene targeting, and, surprisingly, homozygotes die during the periimplantation stage [4].
  • In addition, Brg1 heterozygotes are predisposed to exencephaly and tumors [4].
  • Within this complex, the BRM (SNF2alpha) and BRG1 (SNF2beta) proteins are mutually exclusive subunits that are believed to affect nucleosomal structures using the energy of ATP hydrolysis [5].

Anatomical context of Smarca4

  • To further investigate the in vivo role of BRG1, we selectively ablated Brg1 in keratinocytes of the forming mouse epidermis [6].
  • By contrast, as Brg1-null fibroblasts are viable but Brg1-null embryos die during the peri-implantation stage, BRG1 might exert cell-specific functions [6].
  • In addition, Brg1 is expressed in cells within the developing skeleton of the mouse embryo as well as in osteoblasts ex vivo [7].
  • Recent biochemical data has linked Brg1 function to genes important for T lymphocyte differentiation [8].
  • However, the Sox2-positive, proliferating neural progenitor cell population was expanded, and expression of a terminally differentiated neuronal marker, N-tubulin, was diminished upon loss of Brg1 activity, suggesting that Brg1 is required for neuronal differentiation [9].

Associations of Smarca4 with chemical compounds

  • We show that F9 EC cells inactivated on both SNF2beta alleles are not viable and that heterozygous mutant cells are affected in proliferation but not in RA-induced differentiation [10].
  • The DEX-activated promoter possessed similar composition as the basal promoter, but also contains stably bound Brg1 [11].

Physical interactions of Smarca4


Regulatory relationships of Smarca4

  • Consistent with this, dominant-negative interference with Brg1 function in P19 cells suppressed neuronal differentiation promoted by NeuroD2, showing the requirement of Brg1 for neuronal differentiation is conserved in mammalian cells [9].

Other interactions of Smarca4


  1. A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development. Bultman, S.J., Gebuhr, T.C., Magnuson, T. Genes Dev. (2005) [Pubmed]
  2. SWI/SNF chromatin-remodeling factors induce changes in DNA methylation to promote transcriptional activation. Banine, F., Bartlett, C., Gunawardena, R., Muchardt, C., Yaniv, M., Knudsen, E.S., Weissman, B.E., Sherman, L.S. Cancer Res. (2005) [Pubmed]
  3. Maternal BRG1 regulates zygotic genome activation in the mouse. Bultman, S.J., Gebuhr, T.C., Pan, H., Svoboda, P., Schultz, R.M., Magnuson, T. Genes Dev. (2006) [Pubmed]
  4. A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Bultman, S., Gebuhr, T., Yee, D., La Mantia, C., Nicholson, J., Gilliam, A., Randazzo, F., Metzger, D., Chambon, P., Crabtree, G., Magnuson, T. Mol. Cell (2000) [Pubmed]
  5. Altered control of cellular proliferation in the absence of mammalian brahma (SNF2alpha). Reyes, J.C., Barra, J., Muchardt, C., Camus, A., Babinet, C., Yaniv, M. EMBO J. (1998) [Pubmed]
  6. 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. Indra, A.K., Dupé, V., Bornert, J.M., Messaddeq, N., Yaniv, M., Mark, M., Chambon, P., Metzger, D. Development (2005) [Pubmed]
  7. SWI/SNF chromatin remodeling complex is obligatory for BMP2-induced, Runx2-dependent skeletal gene expression that controls osteoblast differentiation. Young, D.W., Pratap, J., Javed, A., Weiner, B., Ohkawa, Y., van Wijnen, A., Montecino, M., Stein, G.S., Stein, J.L., Imbalzano, A.N., Lian, J.B. J. Cell. Biochem. (2005) [Pubmed]
  8. The role of Brg1, a catalytic subunit of mammalian chromatin-remodeling complexes, in T cell development. Gebuhr, T.C., Kovalev, G.I., Bultman, S., Godfrey, V., Su, L., Magnuson, T. J. Exp. Med. (2003) [Pubmed]
  9. The SWI/SNF chromatin remodeling protein Brg1 is required for vertebrate neurogenesis and mediates transactivation of Ngn and NeuroD. Seo, S., Richardson, G.A., Kroll, K.L. Development (2005) [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. Formation of higher-order secondary and tertiary chromatin structures by genomic mouse mammary tumor virus promoters. Georgel, P.T., Fletcher, T.M., Hager, G.L., Hansen, J.C. Genes Dev. (2003) [Pubmed]
  12. T helper type 1-specific Brg1 recruitment and remodeling of nucleosomes positioned at the IFN-gamma promoter are Stat4 dependent. Zhang, F., Boothby, M. J. Exp. Med. (2006) [Pubmed]
  13. Skeletal muscle specification by myogenin and Mef2D via the SWI/SNF ATPase Brg1. Ohkawa, Y., Marfella, C.G., Imbalzano, A.N. EMBO J. (2006) [Pubmed]
  14. Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes. Vradii, D., Wagner, S., Doan, D.N., Nickerson, J.A., Montecino, M., Lian, J.B., Stein, J.L., van Wijnen, A.J., Imbalzano, A.N., Stein, G.S. J. Cell. Physiol. (2006) [Pubmed]
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