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المؤلفNasipak, Brian T.
المؤلفPadilla-Benavides, Teresita
المؤلفGreen, Karin M.
المؤلفLeszyk, John D.
المؤلفMao, Wenjie
المؤلفKonda, Silvana
المؤلفSif, Said
المؤلفShaffer, Scott A.
المؤلفOhkawa, Yasuyuki
المؤلفImbalzano, Anthony N.
تاريخ الإتاحة2016-11-13T10:02:24Z
تاريخ النشر2015-06-17
اسم المنشورNature Communications
المعرّفhttp://dx.doi.org/10.1038/ncomms8441
الاقتباسNasipak, B. T. et al. Opposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme. Nat. Commun. 6:7441 (2015)
معرّف المصادر الموحدhttp://hdl.handle.net/10576/4990
الملخصCalcium 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.
راعي المشروعNIH grant GM56244
اللغةen
الناشرNature Publishing Group
الموضوعMusculoskeletal system
Chromatin remodelling
Calcium signalling
Differentiation
العنوانOpposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme
النوعArticle
رقم المجلد6
ESSN2041-1723


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