title: Enhancer of polycomb1, a novel homeodomain only protein-binding partner, induces skeletal muscle differentiation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kee
authors.forename: Ju-Ryoung
authors.initials: JR
authors.lastname: Kim
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Nam
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Park
authors.forename: Sera
authors.initials: S
authors.lastname: Shin
authors.forename: Jeong Chul
authors.initials: JC
authors.lastname: Kim
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimono
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
authors.forename: Nacksung
authors.initials: N
authors.lastname: Kim
authors.forename: Kyung Keun
authors.initials: KK
authors.lastname: Kim
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
mesh_terms: 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
chemical_list: C496700:Epc1 protein, mouse; D018398:Homeodomain Proteins; C466740:Hop protein, mouse; D012097:Repressor Proteins