Alternative titles; symbols
HGNC Approved Gene Symbol: SMARCD3
Cytogenetic location: 7q36.1 Genomic coordinates (GRCh38): 7:151,238,780-151,277,149 (from NCBI)
Chromatin is actively remodeled during development. Chromatin remodeling of certain genes appears to precede their transcriptional activation. In yeast, the multisubunit SWI/SNF complex is thought to be responsible for chromatin remodeling. Wang et al. (1996) isolated an analogous SWI/SNF complex from the human YT cell line. They found that the resultant complexes are composed of 9 to 12 polypeptides, which they termed BAFs (for BRG1-associated factors). Wang et al. (1996) cloned BAF60c based on its homology with BAF60a (601735). BAF60c encodes a polypeptide of 469 amino acids and is homologous to the yeast SWP73 gene, a component of the yeast SWI/SNF chromatin remodeling complex. The human genes BAF60a (601735), BAF60b (601736), and BAF60c are highly homologous.
See also BAF155 (601732) and BAF170 (601734), other subunits in this complex.
Lickert et al. (2004) found mouse Smarcd3 to be expressed specifically in the heart and somites of the early mouse embryo. Smarcd3 silencing by RNA interference in mouse embryos caused defects in heart morphogenesis, reflecting impaired expansion of the anterior/secondary heart field, and also caused abnormal cardiac and skeletal muscle differentiation. An intermediate reduction in Smarcd3 expression led to defects in outflow tract remodeling reminiscent of human congenital heart defects. When overexpressed in cell culture, Smarcd3 mediated interactions between cardiac transcription factors and Brg1 (SMARCA4; 603254), thereby potentiating the activation of target genes. Lickert et al. (2004) concluded that SMARCD3 shows tissue-specific and dose-dependent effects in recruiting BAF chromatin remodeling complexes to specific enhancers, ensuring transcriptional regulation during organogenesis.
Takeuchi and Bruneau (2009) defined the minimal requirements for transdifferentiation of mouse mesoderm to cardiac myocytes. They showed that 2 cardiac transcription factors, Gata4 (600576) and Tbx5 (601620), and a cardiac-specific subunit of BAF chromatin-remodeling complexes, Baf60c, can direct ectopic differentiation of mouse mesoderm into beating cardiomyocytes, including the normally noncardiogenic posterior mesoderm and the extraembryonic mesoderm of the amnion. Gata4 and Baf60c initiated ectopic cardiac gene expression. Addition of Tbx5 allowed differentiation into contracting cardiomyocytes and repression of noncardiac mesodermal genes. Baf60c was essential for the ectopic cardiogenic activity of Gata4 and Tbx5, partly by permitting binding of Gata4 to cardiac genes, indicating a novel instructive role for BAF complexes in tissue-specific regulation. Takeuchi and Bruneau (2009) concluded that the combined function of these factors establishes a robust mechanism for controlling cellular differentiation, and may allow reprogramming of new cardiomyocytes for regenerative purposes.
By PCR of a somatic cell hybrid panel and radiation hybrid analysis, Ring et al. (1998) mapped the SMARCD3 gene to chromosome 7q35-q36.
Lickert, H., Takeuchi, J. K., von Both, I., Walls, J. R., McAuliffe, F., Adamson, S. L., Henkelman, R. M., Wrana, J. L., Rossant, J., Bruneau, B. G. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature 432: 107-112, 2004. [PubMed: 15525990] [Full Text: https://doi.org/10.1038/nature03071]
Ring, H. Z., Vameghi-Meyers, V., Wang, W., Crabtree, G. R., Francke, U. Five SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin (SMARC) genes are dispersed in the human genome. Genomics 51: 140-143, 1998. [PubMed: 9693044] [Full Text: https://doi.org/10.1006/geno.1998.5343]
Takeuchi, J. K., Bruneau, B. G. Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 459: 708-711, 2009. [PubMed: 19396158] [Full Text: https://doi.org/10.1038/nature08039]
Wang, W., Xue, Y., Zhou, S., Kuo, A., Cairns, B. R., Crabtree, G. R. Diversity and specialization of mammalian SWI/SNF complexes. Genes Dev. 10: 2117-2130, 1996. [PubMed: 8804307] [Full Text: https://doi.org/10.1101/gad.10.17.2117]