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J Cell Biol. 2014 Jun 23;205(6):829-46. doi: 10.1083/jcb.201403021. Epub 2014 Jun 16.

The Cavβ1a subunit regulates gene expression and suppresses myogenin in muscle progenitor cells.

Author information

1
Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157.
2
Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157 Biochemistry Research Institute of La Plata (INIBIOLP)/National Scientific and Technical Research Council (CONICET), School of Medicine, National University of La Plata, 1900 La Plata, BA, Argentina.
3
Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157.
4
Biochemistry Research Institute of La Plata (INIBIOLP)/National Scientific and Technical Research Council (CONICET), School of Medicine, National University of La Plata, 1900 La Plata, BA, Argentina.
5
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794.
6
Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157 odelbono@wakehealth.edu.

Abstract

Voltage-gated calcium channel (Cav) β subunits are auxiliary subunits to Cavs. Recent reports show Cavβ subunits may enter the nucleus and suggest a role in transcriptional regulation, but the physiological relevance of this localization remains unclear. We sought to define the nuclear function of Cavβ in muscle progenitor cells (MPCs). We found that Cavβ1a is expressed in proliferating MPCs, before expression of the calcium conducting subunit Cav1.1, and enters the nucleus. Loss of Cavβ1a expression impaired MPC expansion in vitro and in vivo and caused widespread changes in global gene expression, including up-regulation of myogenin. Additionally, we found that Cavβ1a localizes to the promoter region of a number of genes, preferentially at noncanonical (NC) E-box sites. Cavβ1a binds to a region of the Myog promoter containing an NC E-box, suggesting a mechanism for inhibition of myogenin gene expression. This work indicates that Cavβ1a acts as a Cav-independent regulator of gene expression in MPCs, and is required for their normal expansion during myogenic development.

PMID:
24934157
PMCID:
PMC4068134
DOI:
10.1083/jcb.201403021
[Indexed for MEDLINE]
Free PMC Article

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