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ȣ - 490294 208 |
| Homeodomain only protein, HOP, interacts with Enhancer of Polycomb1 to regulate cardiomyoblast survivals and cardiac gene transcription |
| ¹Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, ²Department of Pathology, Nagoya University School of Medicine, Japan, ³Cardiovascular Division, University of Pennsylvania, Philadelphia, PA, USA |
| ¹Jung Mi Yang, ¹Hye Young Park, ¹Hae Jin Kee, ¹Sera Shin, ²Yohei Shimono, ²Masahide Takahashi, ¹Kyung Keun Kim, ³Jonathan A. Epstein, ¹Hyun Kook |
HOP, a recently discovered homeodomain only protein, is an unusual homeodomain protein and is expressed in embryonic and postnatal cardiac myocytes. Though HOP does not bind to DNA, it acts as a co-repressor of serum response factor (SRF)-dependent cardiac specific gene. Here we show that HOP also interacts with Enhancer of Polycomb (EPC1), a murine homolog of a Drosophila polycomb gene thought to function in chromatin remodeling and transcriptional repression. Yeast-two hybrid assays using a human adult heart library revealed that the HOP can associate with EPC1. Amino terminal domain of EPC1 as well as full EPC1 physically interacts with HOP in mammalian cells. Northern blot analysis indicates that a 4 kb EPC1 transcript is highly expressed in mouse heart. HOP colocalizes with EPC1 in the nucleus of H9c2 cells. EPC1 and HOP synergistically reduced the H9c2 cell survivals and caused actin rearrangement. Transfection of higher doses of EPC1 caused significant reduction of luciferase activity of atrial natriuretic factor, myosin light chain 2v,Α-cardiac actin, smooth muscle 22Α, and serum response factor promoters. These results suggest that HOP may be involved in epigenetic gene regulation in the heart-specific genes.
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