Exploring the Regulation of Tmem182 Gene Expression in the Context of Retinoid X Receptor Signaling

We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor (RXR), promotes the differentiation and fusion of skeletal myoblasts. We have also analyzed the genomic programs underlying rexinoid-enhanced myogenic differentiation to identify novel regulatory pathways. As such, we observed a significant upregulation of a transcript encoding a predicted transmembrane protein, Tmem182, during C2C12 myoblast differentiation. Despite the documentation of <i>Tmem182</i> expression in skeletal muscles, its regulation had yet to be explored. Here, we show that <i>Tmem182</i> gene expression is markedly augmented in early myoblast differentiation and further enhanced by RXR signaling. In addition, <i>Tmem182</i> expression is specific to muscle tissues and related to muscle master regulator MyoD. We found that MyoD and histone acetyltransferase p300 are bound to the <i>Tmem182</i> promoter, and <i>Tmem182</i> expression is p300-dependent. Thus, our data display a putative epigenetic signature associated with p300 and histone acetylation in rexinoid-responsive locus activation and transcription of myogenic targets.