Opposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme
Academic Program
NeuroscienceUMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyProteomics and Mass Spectrometry Facility
Department of Cell and Developmental Biology
Document Type
Journal ArticlePublication Date
2015-06-17Keywords
Biological sciencesCell biology
Developmental biology
Cell Biology
Computational Biology
Developmental Biology
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Show full item recordAbstract
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.Source
Nat Commun. 2015 Jun 17;6:7441. doi: 10.1038/ncomms8441. Link to article on publisher's siteDOI
10.1038/ncomms8441Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26483PubMed ID
26081415Related Resources
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