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 Tmem182 expression in skeletal muscles, its regulation had yet to be explored. Here, we show that Tmem182 gene expression is markedly augmented in early myoblast differentiation and further enhanced by RXR signaling. In addition, Tmem182 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 Tmem182 promoter, and Tmem182 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.