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    Opposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme

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    Authors
    Nasipak, Brian T.
    Padilla-Benavides, Teresita
    Green, Karin M.
    Leszyk, John D.
    Mao, Wenjie
    Konda, Silvana
    Sif, Said
    Shaffer, Scott A.
    Ohkawa, Yasuyuki
    Imbalzano, Anthony N.
    Student Authors
    Wenjie Mao
    Academic Program
    Neuroscience
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Proteomics and Mass Spectrometry Facility
    Department of Cell and Developmental Biology
    Document Type
    Journal Article
    Publication Date
    2015-06-17
    Keywords
    Biological sciences
    Cell biology
    Developmental biology
    Cell Biology
    Computational Biology
    Developmental Biology
    
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    http://dx.doi.org/10.1038/ncomms8441
    Abstract
    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 site
    DOI
    10.1038/ncomms8441
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/26483
    PubMed ID
    26081415
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1038/ncomms8441
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