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.
| Original language | English |
|---|---|
| Article number | e00063-19 |
| Journal | Molecular and cellular biology |
| Volume | 39 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - Oct 1 2019 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
Cite this
Calcineurin broadly regulates the initiation of skeletal muscle-specific gene expression by binding target promoters and facilitating the interaction of the SWI/SNF chromatin remodeling enzyme. / Witwicka, Hanna; Nogami, Jumpei; Syed, Sabriya A.; Maehara, Kazumitsu; Padilla-Benavides, Teresita; Ohkawa, Yasuyuki; Imbalzano, Anthony N.
In: Molecular and cellular biology, Vol. 39, No. 19, e00063-19, 01.10.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Calcineurin broadly regulates the initiation of skeletal muscle-specific gene expression by binding target promoters and facilitating the interaction of the SWI/SNF chromatin remodeling enzyme
AU - Witwicka, Hanna
AU - Nogami, Jumpei
AU - Syed, Sabriya A.
AU - Maehara, Kazumitsu
AU - Padilla-Benavides, Teresita
AU - Ohkawa, Yasuyuki
AU - Imbalzano, Anthony N.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85072134409&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072134409&partnerID=8YFLogxK
U2 - 10.1128/MCB.00063-19
DO - 10.1128/MCB.00063-19
M3 - Article
C2 - 31308130
AN - SCOPUS:85072134409
VL - 39
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 19
M1 - e00063-19
ER -