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Article: SWI/SNF protein component BAF250a regulates cardiac progenitor cell differentiation by modulating chromatin accessibility during second heart field development

TitleSWI/SNF protein component BAF250a regulates cardiac progenitor cell differentiation by modulating chromatin accessibility during second heart field development
Authors
Issue Date2012
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal of Biological Chemistry, 2012, v. 287 n. 29, p. 24255-24262 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/149063
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLei, Len_US
dc.contributor.authorGao, Xen_US
dc.contributor.authorSham, MHen_US
dc.contributor.authorWang, Zen_US
dc.date.accessioned2012-06-22T06:19:39Z-
dc.date.available2012-06-22T06:19:39Z-
dc.date.issued2012en_US
dc.identifier.citationJournal of Biological Chemistry, 2012, v. 287 n. 29, p. 24255-24262en_US
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/149063-
dc.description.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.-
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/-
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.-
dc.subject.meshCell Differentiation - genetics - physiology-
dc.subject.meshChromatin - metabolism-
dc.subject.meshChromosomal Proteins, Non-Histone - genetics - metabolism-
dc.subject.meshDNA-Binding Proteins - genetics - metabolism-
dc.subject.meshNuclear Proteins - genetics - metabolism-
dc.titleSWI/SNF protein component BAF250a regulates cardiac progenitor cell differentiation by modulating chromatin accessibility during second heart field developmenten_US
dc.typeArticleen_US
dc.identifier.emailSham, MH: mhsham@hku.hken_US
dc.identifier.emailWang, Z: zhwang@partners.org-
dc.identifier.authoritySham, MH=rp00380en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M112.365080-
dc.identifier.pmid22621927-
dc.identifier.pmcidPMC3397851-
dc.identifier.scopuseid_2-s2.0-84863811009-
dc.identifier.hkuros200414en_US
dc.identifier.volume287en_US
dc.identifier.issue29-
dc.identifier.spage24255-
dc.identifier.epage24262-
dc.identifier.eissn1083-351X-
dc.identifier.isiWOS:000306651100019-
dc.publisher.placeUnited States-

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