Enhancer of polycomb1, a novel homeodomain only protein-binding partner, induces skeletal muscle differentiation

Hae Jin Kee, Ju Ryoung Kim, Kwang Il Nam, Young Park Hye, Sera Shin, Chul Kim Jeong, Yohei Shimono, Masahide Takahashi, Ho Jeong Myung, Nacksung Kim, Keun Kim Kyung, Hyun Kook

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7700-7709
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number10
DOIs
Publication statusPublished - 02-03-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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