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SWI/SNF protein component BAF250a regulates cardiac progenitor cell differentiation by modulating chromatin accessibility during second heart field development
Lei I.1; Gao X.1; Sham M.H.3; Wang Z.1
2012-07-13
Source PublicationJournal of Biological Chemistry
ISSN00219258 1083351X
Volume287Issue:29Pages:24255-24262
AbstractATP-dependent SWI/SNF chromatin remodeling complexes alter the structure of chromatin at specific loci and facilitate tissue-specific gene regulation during development. Several SWI/SNF subunits are required for cardiogenesis. However, the function and mechanisms of SWI/SNF in mediating cardiac progenitor cell (CPC) differentiation during cardiogenesis are not well understood. Our studies of the SWI/SNF chromatin remodeling complex identified that BAF250a, a regulatory subunit of the SWI/SNF, plays a key role in CPC differentiation. BAF250a ablation in mouse second heart field (SHF) led to trabeculation defects in the right ventricle, ventricular septal defect, persistent truncus arteriosus, reduced myocardial proliferation, and embryonic lethality around E13. Using an embryonic stem cell culture system that models the formation and differentiation of SHF CPCs in vivo, we have shown that BAF250a ablation in CPCs specifically inhibits cardiomyocyte formation. Moreover, BAF250a selectively regulates the expression of key cardiac factors Mef2c, Nkx2.5, and Bmp10 in SHF CPCs. Chromatin immunoprecipitation and DNase I digestion assays indicate that BAF250a regulates gene expression by binding selectively to its target gene promoters and recruiting Brg1, the catalytic subunit of SWI/SNF, to modulate chromatin accessibility. Our results thus identify BAF250a-mediated chromatin remodeling as an essential epigenetic mechanism mediating CPC differentiation. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI10.1074/jbc.M112.365080
URLView the original
Language英語
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Cited Times [WOS]:37   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Massachusetts General Hospital
2.Harvard Stem Cell Institute
3.The University of Hong Kong Li Ka Shing Faculty of Medicine
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Lei I.,Gao X.,Sham M.H.,et al. SWI/SNF protein component BAF250a regulates cardiac progenitor cell differentiation by modulating chromatin accessibility during second heart field development[J]. Journal of Biological Chemistry,2012,287(29):24255-24262.
APA Lei I.,Gao X.,Sham M.H.,&Wang Z..(2012).SWI/SNF protein component BAF250a regulates cardiac progenitor cell differentiation by modulating chromatin accessibility during second heart field development.Journal of Biological Chemistry,287(29),24255-24262.
MLA Lei I.,et al."SWI/SNF protein component BAF250a regulates cardiac progenitor cell differentiation by modulating chromatin accessibility during second heart field development".Journal of Biological Chemistry 287.29(2012):24255-24262.
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