BRG1/BRM-associated factor complex subunit diversity promotes temporally distinct gene expression programs in cardiogenesis [article]

Swetansu Hota, Jeffrey Johnson, Erik Verschueren, Yiwen Zhu, Xin Sun, Len Pennacchio, Janet Rossant, Nevan Krogan, Benoit Bruneau
2017 bioRxiv   pre-print
Chromatin remodeling complexes instruct cellular differentiation and lineage specific transcription. However, the underlying mechanism is unclear. Here, using immunoprecipitation with mass spectrometry (IP-MS), we determined the dynamic composition of the BRG1/BRM associated factor (BAF) complexes during mammalian cardiac differentiation, and identified BAF60c (SMARCD3) and BAF170 (SMARCC2) as subunits enriched in cardiac precursors (CP) and cardiomyocytes (CM). The catalytic subunit Brg1 has a
more » ... specific role in CPs to initiate cardiac gene expression programs and repress non-cardiac fates, a role shared by Baf60c and Baf170. In CMs, BAF60c and BAF170 are found in BRG1 and BRM-associated complexes, and are essential for maintaining the cardiac program, largely by repressing non-cardiac gene expression. BAF60c and BAF170 both modulate BAF complex composition and stoichiometry. In CM, BAF170 facilitates expulsion of a subset of BRG1-containing complexes near genes regulating post-transcriptional and epigenetic modification, as opposed to those evicted independent of BAF170 that regulate transcription, growth and development. Thus, BAF complexes use varied interdependent mechanisms to direct temporal gene expression programs in cardiogenesis.
doi:10.1101/166983 fatcat:7nvsowlk6jhutk5uiwumy6diiu