Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function
Hota, Swetansu K.
Seidman, Christine E.
Seidman, J. G.
Gregorio, Carol C.
Henkelman, R. Mark
Bruneau, Benoit G.
AffiliationUniv Arizona, Dept Cellular & Mol Med
MetadataShow full item record
PublisherCOMPANY OF BIOLOGISTS LTD
CitationCardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function 2018, 7 (1):bio029512 Biology Open
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AbstractHow chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example, Baf60c (Smarcd3) 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 Baf60c leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of Baf60c in cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function. Baf60c 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 Baf60c 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.
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VersionFinal published version
SponsorsNational Institutes of Health [R01HL085860, P01HL089707, UM1HL098179, R01HL108625]; California Institute of Regenerative Medicine [RN2-00903]; Lawrence J. and Florence A. DeGeorge Charitable Trust/American Heart Association Established Investigator Award [090008N]; American Heart Association [13POST17290043]; Tobacco-Related Disease Research Program [22FT-0079]; NIH/National Center for Research Resources grant [C06 RR018928]; Younger Family Fund