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 polycomb1 (Epc1), a chromatin protein, can modulate skeletal muscle differentiation, although the mechanisms of this action have yet to be defined. Here we report that Epc1 recruits both serum response factor (SRF) and p300 to induce skeletal muscle differentiation. Epc1 interacted physically with SRF. Transfection of Epc1 to myoblast cells potentiated the SRF-induced expression of skeletal muscle-specific genes as well as multinucleation. Proximal CArG box in the skeletal alpha-actin promoter was responsible for the synergistic activation of the promoter-luciferase. Epc1 knockdown caused a decrease in the acetylation of histones associated with serum response element (SRE) of the skeletal alpha-actin promoter. The Epc1.SRF complex bound to the SRE, and the knockdown of Epc1 resulted in a decrease in SRF binding to the skeletal alpha-actin promoter. Epc1 recruited histone acetyltransferase activity, which was potentiated by cotransfection with p300 but abolished by si-p300. Epc1 directly bound to p300 in myoblast cells. Epc1+/- mice showed distortion of skeletal alpha-actin, and the isolated myoblasts from the mice had impaired muscle differentiation. These results suggest that Epc1 is required for skeletal muscle differentiation by recruiting both SRF and p300 to the SRE of muscle-specific gene promoters.
Kim
Ju-Ryoung
JR
From the Medical Research Center for Gene Regulation, Gwangju 501-746; Departments of Pharmacology, Gwangju 501-746.
Kee
Hae Jin
HJ
From the Medical Research Center for Gene Regulation, Gwangju 501-746; Departments of Pharmacology, Gwangju 501-746; BK 21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746.
Kim
Ji-Young
JY
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-745, South Korea.
Joung
Hosouk
H
From the Medical Research Center for Gene Regulation, Gwangju 501-746; BK 21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746.
Nam
Kwang-Il
KI
BK 21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746; Anatomy, Gwangju 501-746.
Eom
Gwang Hyeon
GH
From the Medical Research Center for Gene Regulation, Gwangju 501-746; Departments of Pharmacology, Gwangju 501-746.
Choe
Nakwon
N
From the Medical Research Center for Gene Regulation, Gwangju 501-746; Departments of Pharmacology, Gwangju 501-746.
Kim
Hyung-Suk
HS
BK 21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746; Forensic Medicine, Gwangju 501-746.
Kim
Jeong Chul
JC
Departments of Surgery, Gwangju 501-746.
Kook
Hoon
H
Pediatrics, Chonnam National University Hospital, Gwangju 501-746.
Seo
Sang Beom
SB
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-745, South Korea.
Kook
Hyun
H
From the Medical Research Center for Gene Regulation, Gwangju 501-746; Departments of Pharmacology, Gwangju 501-746; BK 21 Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746. Electronic address: kookhyun@chonnam.ac.kr.
D000107:Acetylation; D000199:Actins / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology; D006579:Heterozygote; D006657:Histones / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D026362:Serum Response Factor / Q000378:metabolism*
D000199:Actins; C496700:Epc1 protein, mouse; D006657:Histones; D012097:Repressor Proteins; D026362:Serum Response Factor; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse