The Ca_vβ_1a subunit regulates gene expression and suppresses myogenin in muscle progenitor cells

Voltage-gated calcium channel (Ca_v) β subunits are auxiliary subunits to Ca_vs. 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 Ca_vβ in muscle progenitor cells (MPCs). We found that Ca_vβ_1a is expressed in proliferating MPCs, before expression of the calcium conducting subunit Ca_v1.1, and enters the nucleus. Loss of Ca_vβ_1a 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 Ca_vβ_1a localizes to the promoter region of a number of genes, preferentially at noncanonical (NC) E-box sites. Ca_vβ_1a 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 Ca_vβ_1a acts as a Ca_v-independent regulator of gene expression in MPCs, and is required for their normal expansion during myogenic development.