title: The Cavβ1a subunit regulates gene expression and suppresses myogenin in muscle progenitor cells.
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.
authors.affiliation: 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.
authors.forename: Jackson
authors.initials: J
authors.lastname: Taylor
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pereyra
authors.affiliation: Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Tan
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Messi
authors.affiliation: Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hereñú
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Pei-Fen
authors.initials: PF
authors.lastname: Kuan
authors.affiliation: 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.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Delbono
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D032446:Myoblasts / Q000378:metabolism*; D018008:Myogenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C492923:Cacnb1 protein, mouse; D020746:Calcium Channels, L-Type; D002843:Chromatin; D018008:Myogenin