Abstract:
:Calcineurin (Cn) is a calcium-activated serine/threonine protein phosphatase that is broadly implicated in diverse cellular processes, including the regulation of gene expression. During skeletal muscle differentiation, Cn activates the nuclear factor of activated T-cell (NFAT) transcription factor but also promotes differentiation by counteracting the negative influences of protein kinase C beta (PKCβ) via dephosphorylation and activation of Brg1, an enzymatic subunit of the mammalian SWI/SNF ATP-dependent chromatin remodeling enzyme. Here we identified four major temporal patterns of Cn-dependent gene expression in differentiating myoblasts and determined that Cn is broadly required for the activation of the myogenic gene expression program. Mechanistically, Cn promotes gene expression through direct binding to myogenic promoter sequences and facilitating the binding of Brg1, other SWI/SNF subunit proteins, and MyoD, a critical lineage determinant for skeletal muscle differentiation. We conclude that the Cn phosphatase directly impacts the expression of myogenic genes by promoting ATP-dependent chromatin remodeling and formation of transcription-competent promoters.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Witwicka H,Nogami J,Syed SA,Maehara K,Padilla-Benavides T,Ohkawa Y,Imbalzano ANdoi
10.1128/MCB.00063-19subject
Has Abstractpub_date
2019-09-11 00:00:00issue
19eissn
0270-7306issn
1098-5549pii
MCB.00063-19journal_volume
39pub_type
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