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AuthorNasipak, Brian T.
AuthorPadilla-Benavides, Teresita
AuthorGreen, Karin M.
AuthorLeszyk, John D.
AuthorMao, Wenjie
AuthorKonda, Silvana
AuthorSif, Said
AuthorShaffer, Scott A.
AuthorOhkawa, Yasuyuki
AuthorImbalzano, Anthony N.
Available date2016-11-13T10:02:24Z
Publication Date2015-06-17
Publication NameNature Communicationsen_US
Identifierhttp://dx.doi.org/10.1038/ncomms8441
CitationNasipak, B. T. et al. Opposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme. Nat. Commun. 6:7441 (2015)
URIhttp://hdl.handle.net/10576/4990
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 β (PKCβ) 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.
SponsorNIH grant GM56244
Languageen
PublisherNature Publishing Group
SubjectMusculoskeletal system
SubjectChromatin remodelling
SubjectCalcium signalling
SubjectDifferentiation
TitleOpposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme
TypeArticle
Volume Number6
ESSN2041-1723


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