The Ca(v)β(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(v)s. Recent reports show Ca(v)β 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(v)β in muscle progenitor cells (MPCs). We found that Ca(v)β(1a) is expressed in proliferating MPCs, before expression of the calcium conducting subunit Ca(v)1.1, and enters the nucleus. Loss of Ca(v)β(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(v)β(1a) localizes to the promoter region of a number of genes, preferentially at noncanonical (NC) E-box sites. Ca(v)β(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(v)β(1a) acts as a Ca(v)-independent regulator of gene expression in MPCs, and is required for their normal expansion during myogenic development.