Dynamic BAF chromatin remodeling complex subunit inclusion promotes temporally distinct gene expression programs in cardiogenesis

ABSTRACT: Chromatin remodeling complexes instruct cellular differentiation and lineage specific transcription. The BRG1/BRM associated factor (BAF) complexes are important for several aspects of differentiation. We show that the catalytic subunit Brg1 has a specific role in cardiac precursors (CPs) to initiate cardiac gene expression programs and repress non-cardiac expression. Using immunoprecipitation immunopurification with mass spectrometry we determined the dynamic composition of BAF complexes during mammalian cardiac differentiation, identifying several cell-type specific subunits. We focused on the CP- and cardiomyocytes (CM)-enriched subunits BAF60c (SMARCD3) and BAF170 (SMARCC2). Baf60c and Baf170 co-regulate gene expression with Brg1 in CPs, and in CMs their loss results in broadly deregulated cardiac gene expression. BRG1, BAF60, and BAF170 modulate chromatin accessibility, to either promote accessibility at activated genes, while closing up chromatin at repressed genes. BAF60c and BAF170 are required for proper BAF complex composition, and BAF170 loss leads to retention of BRG1 at CP-specific enhancers. Thus, dynamic interdependent BAF complex subunit assembly modulates chromatin states and thereby participates in directing temporal gene expression programs in cardiogenesis.

OTHER RELATED OMICS DATASETS IN: GSE116296 GSE116295 GSE116286 GSE116279 GSE116281

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Stem Cell

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Jeffrey Johnson  

LAB HEAD: Nevan Krogan

PROVIDER: PXD012721 | Pride | 2019-11-13

REPOSITORIES: Pride