2003 Fiscal Year Final Research Report Summary
Chromatin dynamics and regulation of cell-differentiation
| Project/Area Number |
14208078
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | RIKEN |
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Principal Investigator |
YOKOYAMA Kazunari RIKEN, Gene Engineering Division, Head, 遺伝子材料開発室, 室長(副主任研究員待遇) (80182707)
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| Co-Investigator(Kenkyū-buntansha) |
潘 建治 独立行政法人理化学研究所, 遺伝子材料開発室, 協力研究員
UGAI Hideyo RIKEN, Gene Engineering Division, Technical researcher, 遺伝子材料開発室, 技師(研究職) (00344060)
MURATA Takehide RIKEN, Gene Engineering Division, Senior researcher, 遺伝子材料開発室, 先任研究員 (50281621)
HATAMA Shinichi RIKEN, Gene Engineering Division, Cooperative researcher, 遺伝子材料開発室, 協力研究員
SHINOZUKA Yoriko RIKEN, Gene Engineering Division, Cooperative researcher, 遺伝子材料開発室, 協力研究員
PAN Jianzhi RIKEN, Gene Engineering Division, Cooperative researcher
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| Project Period (FY) |
2002 – 2003
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| Keywords | Chromatin / JDP2 / AP-1 / Cell-differentiation / EC cells / Retinoic aid / Histone / Deacetylase |
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| Research Abstract |
Up-regulation of the c-jun gene is a critical role in the retinoic acid (RA)-induced or adenovirus E1A-induced differentiation of embryonic carcinoma F9 cells. We have characterized an element (differentiation response element, DRE) in the promoter region of the c-jun gene that is both necessary and sufficient for RA and E1A mediated up-regulation of c-jun gene expression during the differentiation of F9 cells. Activation transcription factor (ATF-2), adenovirus E1A associated protein (p300) and Jun dimerization protein (JDP2) cooperated in the regulation of transcription of the c-jun gene. JDP2 served as a repressor of AP-1 and inhibited the transcription of the c-jun gene by p300/ATF-2, by recruitment of histone deacetylase complex (HDAC3), thereby repressing the RA-induced transcription of the c-jun gene and then inhibiting the RA-mediated differentiation of F9 cells. Moreover, the chromatin immune precipitation assays showed the JDP2/HDAC 3 complex, which binds to the differentiati
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on response element within the c-jun promoter in undifferentiated F9 cells, was replaced by the p300 complex in response to RA, with as accompanying change in the histone acetylation status of the chromatin, the initiation of transcription of the c-jun gene, and the subsequent differentiation of F9 cells. We also report here that JDP2 binds directly to histones and inhibits the p300-mediated acetylation of histone. The region that includes the amino-terminal 35 amino acids adjacent to the basic region is required for histone-binding activity and the region that includes both histone-binding domain and the basic region is essential for the inhibition of histone acetylation (INHAT). Moreover, assays of nucleosome assembly in vitro demonstrated that JDP2 also has histone chaperon activity. In addition, JDP2 is associated with the modulation of histone acetylation as a result of its intrinsic histone-deacetylation activity, which is insensitive to conventional inhibitors of histone deacetylases (HDACs) and to an inhibitor of the Sir2 family of deacetylases. Mutation analysis revealed that the leucine zipper motif is critical for the HDAC activity of JDP2. These results indicate that the sequence-specific DNA-binding protein JDP2 controls transcription via the direct regulation of the modification of histones and the assembly of the chromatin. Less
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[Publications] Fukuda, K., Abei, M., Ugai, H., Seo, F., Wakayama, M., Murata, T., Todoroki, T., Tanaka, N., Hamada, H., Yokoyarna, K.: "E1A, E1B double-restricted adenovirus as tumor-selective replacing agent for oncolytic gene therapy of gallblatter cancer."Cancer Research. 63. 4434-4440 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Chiu, R., Rey, O., Zheng, J-Q., Twiss, J.L., Song, J., Pang, S., Yokoyama, K.: "Effects of altered expression and localization of cyclophilin A on differentiation of p19 embyonic carcinoma cells."Cellular and Molecular Neurobiology. 23. 929-943 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Saito, S., Sawai, K., Ugai, H., Moriyasu, S., Minamihashi, A., Yamamoto, Y., Hiroyama, H., Kageyama, S., Pan, J., Murata, T., Kobayashi, Y., Obata, Y., Yokoyama, K.: "Generation of cloned calves and transgenic chimeric embryos from bovine embryonic stem-like cells."Biochem.Biophys.Res.Communi.. 309. 104-113 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Jin, C., Li, H., Murata, T., Sun, K., Horikoshi, M., Chiu, R., Yokoyama, K.: "JDP-2, a repressor of AP-1, recruits a histone deacetylase 3 complex to inhibit the retinoic acid-induced differentiation of F9 cells."Mol.Cell.Biol.. 22. 4815-4826 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Takahashi, N., Kawada, T., Yamamoto, T., Gotoh, T., Taimatsu, A., Aoko, N., Kawasaki, H., Taimatsu, A., Yokovama, K., Kamei, Y., Fukushi, T.: "Overexpression and ribozyme-mediated targeting of transcriptional coactivators, CREB-binding protein (CBP) and p300 revealed their indispensable roles in adipocyte differentiation through the regulation of peroxisome proliferator-activated receptor-γ."J.Biol.Chem.. 270. 16906-16912 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Jin, C., Li, H., Horikoshi, M., Sun K.L., Yokovama, K.: "Role of histone acetyltransferase and deacetylase in the retinoic acid-induced differentiation of F9 cells."Food factors for disease prevention and health promotion (ed.By F.Shahidi, C-T, HO, Watanabe, S., Osawa, T.)(ACS, Washington DC., USA). Chapter15. 163-178 (2003)
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「研究成果報告書概要(欧文)」より
