Enhancer of Polycomb1 Acts on Serum Response Factor to Regulate Skeletal Muscle Differentiation.

Skeletal muscle differentiation is well regulated by a series of transcription factors. We reported previously that enhancer of polycombi (Epcl), a chromatin protein, can modulate skeletal muscle differentiation, although the mechanisms of this action have yet to be defined. Here we report that Epcl recruits both serum response factor (SRF) and p300 to induce skeletal muscle differentiation. Epcl interacted physically with SRF. Transfection of Epcl to myoblast cells potentiated the SRF-induced expression of skeletal muscle-specific genes as well as multinucleation. Proximal CArG box in the skeletal α-actin promoter was responsible for the synergistic activation of the promoter-luciferase. Epcl knockdown caused a decrease in the acetylation of histones associated with serum response element (SRE) of the skeletal a-actin promoter. The EpcFSRF complex bound to the SRE, and the knockdown of Epcl resulted in a decrease in SRF binding to the skeletal n-actin promoter. Epcl recruited histone acetyltransferase activity, which was potentiated by cotransfection with p300 but abolished by si-p300. Epcl directly bound to p300 in myoblast cells. Epc1[sup+/-]mice showed distortion of skeletal α-actin, and the isolated myoblasts from the mice had impaired muscle differentiation. These results suggest that Epcl is required for skeletal muscle differentiation by recruiting both SRF and p300 to the SRE of muscle-specific gene promoters. [ABSTRACT FROM AUTHOR]