1. Enhancer of Polycomb1, a Novel Homeodomain Only Protein-binding Partner, Induces Skeletal Muscle Differentiation
- Author
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Jeong Chul Kim, Kwang Il Nam, Sera Shin, Masahide Takahashi, Kyung Keun Kim, Ju-Ryoung Kim, Hyun Kook, Myung Ho Jeong, Nacksung Kim, Yohei Shimono, Hae Jin Kee, and Hye Young Park
- Subjects
Biology ,Biochemistry ,Gene product ,Mice ,Transactivation ,Pregnancy ,Myosin ,medicine ,Animals ,Humans ,Myocyte ,Muscle, Skeletal ,Enhancer ,Molecular Biology ,Myogenin ,Homeodomain Proteins ,Mice, Knockout ,Wound Healing ,Gene Expression Regulation, Developmental ,Skeletal muscle ,Cell Differentiation ,Cell Biology ,Molecular biology ,Repressor Proteins ,medicine.anatomical_structure ,Homeobox ,Female - 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.
- Published
- 2007