Enhancer of polycomb1, a novel homeodomain only protein-binding partner, induces skeletal muscle differentiation.
Homeodomain only protein, Hop, is an unusual small protein that modulates target gene transcription without direct binding to DNA. Here we show that Hop interacts with Enhancer of Polycomb1 (Epc1), a homolog of a Drosophila polycomb group gene product that regulates transcription, to induce the skeletal muscle differentiation. Yeast two-hybrid assay with the human adult heart cDNA library revealed that Hop can associate with Epc1. The amino-terminal domain of Epc1 as well as full Epc1 physically interacted with Hop in mammalian cells and in yeast. Epc1 is highly expressed in the embryonic heart and adult skeletal muscles. Serum deprivation induced differentiation of H9c2, a myoblast cell line, into skeletal myocytes, and Epc1 was up-regulated. Differentiation of H9c2 was induced by Epc1 overexpression, although it was severely impaired in Epc1-knockdown cells. Co-transfection of Hop potentiated Epc1-induced transactivation of myogenin and myotube formation. Hop knock-out mice elicited a decrease in myosin heavy chain and myogenin expressions in skeletal muscle and showed delay in hamstring muscle healing after injury. Differentiation was impaired in skeletal myoblasts from Hop knock-out mice. These results suggest that Epc1 plays a role in the initiation of skeletal muscle differentiation, and its interaction with Hop is required for the full activity.
Kee
Hae Jin
HJ
Medical Research Center for Gene Regulation, Research Institute of Medical Sciences, and Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju 501-746, South Korea.
Kim
Ju-Ryoung
JR
Nam
Kwang-Il
KI
Park
Hye Young
HY
Shin
Sera
S
Kim
Jeong Chul
JC
Shimono
Yohei
Y
Takahashi
Masahide
M
Jeong
Myung Ho
MH
Kim
Nacksung
N
Kim
Kyung Keun
KK
Kook
Hyun
H
D000818:Animals; D002454:Cell Differentiation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000196:embryology*; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014945:Wound Healing
C496700:Epc1 protein, mouse; D018398:Homeodomain Proteins; C466740:Hop protein, mouse; D012097:Repressor Proteins