2007 Fiscal Year Final Research Report Summary
Epigenetic regulation by HP1-SU(Z)12 molecular interaction
| Project/Area Number |
18510172
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
基礎ゲノム科学
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| Research Institution | Kyushu University |
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Principal Investigator |
YAMAMOTO Ken Kyushu University, Medical Institute of Bioregulation, Associate Professor (60274528)
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| Project Period (FY) |
2006 – 2007
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| Keywords | SUZ12 / polycomb / MEP50 / EZH2 / E2F6 / histone H2A / transcription |
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| Research Abstract |
SUZ12 is a Polycomb group protein that forms Polycomb repressive complexes (PRC2/3) together with EED and histone methyltransferase EZH2. Although the essential role of SUZ12 in regulating the activity of the PRC2/3 complexes has been demonstrated, additional function of this protein was suggested. Here, we show that SUZ12 interacts with WD-repeat protein MEP50 in vitro and in vivo. We show that the MEP50 binds histone H2A, selectively among core histones, and mediates transcriptional repression of protein arginine methyltransferase PRMT5, which is known to methylate H2A and H4. These results suggest that SUZ12 might have a role in transcriptional regulation through physical interaction with MEP50 that can be an adaptor between PRMT5 and its substrate H2A. In addition, we identified physical interaction between SUZ12-EZH2 complex and E2F6. This interaction suggests that SUZ12-EZH2 polycomb complex can be recruited onto genome through E2F6 to regulate transcription of its target genes. Because it has been shown that SUZ12 and EZH2 are up-regulated in cancer cells, our findings provide molecular target for cancer therapy.
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