UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Imbalzano Lab

Publication Date

2019-07-15

Document Type

Article Postprint

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry | Cell Biology | Cells | Cellular and Molecular Physiology | Enzymes and Coenzymes | Genetic Phenomena | Musculoskeletal, Neural, and Ocular Physiology

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 NFAT transcription factor but also promotes differentiation by counteracting the negative influences of protein kinase C beta (PKCbeta) 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.

Rights and Permissions

Copyright © 2019 Witwicka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

DOI of Published Version

10.1128/MCB.00063-19

Source

Mol Cell Biol. 2019 Jul 15. pii: MCB.00063-19. doi: 10.1128/MCB.00063-19. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

Molecular and cellular biology

Related Resources

Link to Article in PubMed

PubMed ID

31308130

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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