Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function

Abstract

How chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example, <i>Baf60c</i> (<i>Smarcd3</i>) encodes a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex, but its role in heart development is not fully understood. We found that constitutive loss of <i>Baf60c</i> leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of <i>Baf60c</i> in cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function. <i>Baf60c</i> regulates a gene expression program that includes genes encoding contractile proteins, modulators of sarcomere function, and cardiac metabolic genes. Many of the genes deregulated in <i>Baf60c</i> null embryos are targets of the MEF2/SRF co-factor Myocardin (MYOCD). In a yeast two-hybrid screen, we identified MYOCD as a BAF60c interacting factor; we showed that BAF60c and MYOCD directly and functionally interact. We conclude that Baf60c is essential for coordinating a program of gene expression that regulates the fundamental functional properties of cardiomyocytes.