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dc.contributor.authorNasipak, Brian T.
dc.contributor.authorPadilla-Benavides, Teresita
dc.contributor.authorGreen, Karin M.
dc.contributor.authorLeszyk, John D.
dc.contributor.authorMao, Wenjie
dc.contributor.authorKonda, Silvana
dc.contributor.authorSif, Said
dc.contributor.authorShaffer, Scott A.
dc.contributor.authorOhkawa, Yasuyuki
dc.contributor.authorImbalzano, Anthony N.
dc.date2022-08-11T08:08:03.000
dc.date.accessioned2022-08-23T15:40:48Z
dc.date.available2022-08-23T15:40:48Z
dc.date.issued2015-06-17
dc.date.submitted2015-10-13
dc.identifier.citationNat Commun. 2015 Jun 17;6:7441. doi: 10.1038/ncomms8441. <a href="http://dx.doi.org/10.1038/ncomms8441">Link to article on publisher's site</a>
dc.identifier.issn2041-1723 (Linking)
dc.identifier.doi10.1038/ncomms8441
dc.identifier.pmid26081415
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26483
dc.description.abstractCalcium signalling is important for differentiation-dependent gene expression, but is also involved in other cellular functions. Therefore, mechanisms must exist to distinguish calcium signalling relevant to differentiation. Calcineurin is a calcium-regulated phosphatase that is required for myogenic gene expression and skeletal muscle differentiation. Here, we demonstrate that inhibition of calcineurin blocks chromatin remodelling and that the Brg1 ATPase of the SWI/SNF chromatin remodelling enzyme, which is required for the activation of myogenic gene expression, is a calcineurin substrate. Furthermore, we identify the calcium-regulated classical protein kinase C beta (PKCbeta) as a repressor of myogenesis and as the enzyme that opposes calcineurin function. Replacement of endogenous Brg1 with a phosphomimetic mutant in primary myoblasts inhibits myogenesis, whereas replacement with a non-phosphorylatable mutant allows myogenesis despite inhibition of calcineurin signalling, demonstrating the functionality of calcineurin/PKC-modified residues. Thus, the Brg1 chromatin remodelling enzyme integrates two antagonistic calcium-dependent signalling pathways that control myogenic differentiation.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26081415&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1038/ncomms8441
dc.subjectBiological sciences
dc.subjectCell biology
dc.subjectDevelopmental biology
dc.subjectCell Biology
dc.subjectComputational Biology
dc.subjectDevelopmental Biology
dc.titleOpposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme
dc.typeJournal Article
dc.source.journaltitleNature communications
dc.source.volume6
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1167&amp;context=cellbiology_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cellbiology_pp/168
dc.identifier.contextkey7709835
refterms.dateFOA2022-08-23T15:40:48Z
html.description.abstract<p>Calcium signalling is important for differentiation-dependent gene expression, but is also involved in other cellular functions. Therefore, mechanisms must exist to distinguish calcium signalling relevant to differentiation. Calcineurin is a calcium-regulated phosphatase that is required for myogenic gene expression and skeletal muscle differentiation. Here, we demonstrate that inhibition of calcineurin blocks chromatin remodelling and that the Brg1 ATPase of the SWI/SNF chromatin remodelling enzyme, which is required for the activation of myogenic gene expression, is a calcineurin substrate. Furthermore, we identify the calcium-regulated classical protein kinase C beta (PKCbeta) as a repressor of myogenesis and as the enzyme that opposes calcineurin function. Replacement of endogenous Brg1 with a phosphomimetic mutant in primary myoblasts inhibits myogenesis, whereas replacement with a non-phosphorylatable mutant allows myogenesis despite inhibition of calcineurin signalling, demonstrating the functionality of calcineurin/PKC-modified residues. Thus, the Brg1 chromatin remodelling enzyme integrates two antagonistic calcium-dependent signalling pathways that control myogenic differentiation.</p>
dc.identifier.submissionpathcellbiology_pp/168
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentProteomics and Mass Spectrometry Facility
dc.contributor.departmentDepartment of Cell and Developmental Biology
dc.source.pages7441
dc.contributor.studentWenjie Mao
dc.description.thesisprogramNeuroscience


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