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

Abstract

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