NIH Research Festival
Chromatin remodeling complexes are required for many distinct nuclear processes during replication and transcriptional regulation. The imitation SWI (ISWI) is an ATP-dependent chromatin remodeling complex and is represented by enzymatic subunits Snf2h (Smarca5) and Snf2l (Smarca1). Although studies have shown that Snf2h is essential for early mouse development and survival, it has remained unclear whether Snf2h plays a role in the development of adipose tissue and muscle. By crossing Snf2l-/-;Snf2hf/f mice with Myf5-Cre, which is selectively expressed in precursor cells giving rise to brown adipose tissue (BAT) and skeletal muscle, we demonstrate that Snf2h, but not Snf2l, is essential for adipose tissue and muscle development in mice. We find deletion of ISWI blocks adipogenesis and myogenesis as well as cell type-specific gene expression in isolated cells from BAT and muscle. Mechanistically, ISWI is required for lineage determining transcription factors (LDTFs) binding on enhancers and LDTF-induced activation of enhancers. Furthermore, we show that Snf2h co-localized with CTCF and the genomic binding of CTCF is globally decreased without change of the protein levels in ISWI KO cells. Our findings suggest an important role of ISWI complex in adipose tissue and muscle development. Collectively, this study shows that ISWI is critical for cell differentiation through correct genomic binding of LDFTs.
Scientific Focus Area: Cell Biology
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