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Chromatin dynamics and regulation of cell-differentiation

Research Project

Project/Area Number 14208078
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionRIKEN

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)

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
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥48,100,000 (Direct Cost: ¥37,000,000、Indirect Cost: ¥11,100,000)
Fiscal Year 2003: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2002: ¥32,630,000 (Direct Cost: ¥25,100,000、Indirect Cost: ¥7,530,000)
KeywordsChromatin / JDP2 / AP-1 / Cell-differentiation / EC cells / Retinoic aid / Histone / Deacetylase / F9細胞 / 分化誘導 / 未分化維持 / HDAC3 / ヒストンシャペロン / 脱アセチル化能
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 … More 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

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] K.Fukuda, K.Yokoyama: "E1A, E1B double-restricted adenovirus as tumor-selective replacing agent for oncolytic gene therapy of gallblatter cancer."Cancer Research. 63. 4434-4440 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] R.Chiu, K.Yokoyama: "Effects of altered expression and localization of cyclophilin A on differentiation of p19 embryonic carcinoma cells."Cell.Mol.Neurobiology. 23. 929-943 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Saito, K.Yokoyama: "Generation of cloned calves and transgenic chimeric embryos from bovine embryonic stem-like cells."Biochem.Biophys.Res.Commu.. 309. 104-113 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Yokoyama: "Role of histone modification during the differentiation of embryonic carcinoma F9 cells."Recent Res.Dev.Cancer. 5. 89-100 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] C.Jin, K.Yokoyama: "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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Takahashi, K.Yokoyama: "Overexpression and ribozyme-mediated targetiong 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] C.Jin, K.Yokoyama: "Food factors for disease prevention and health promotion."American chemical Society (F.Shahidi, C-T.Ho, S.Watanabe, T.Osawa). 450 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yokoyama, K.: "Role of histone modification during the differentiation of embryonic carcinoma F9 cells."Recent Res.Dev.Biochem.. 5. 89-100 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jin, C.et al.: "Role of histone acetyltransferase and deacetylase in the retinoic acid-induced differentiation of F9 cells."Food factors for disease prevention and health promotion. 15. 163-178 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Pan, J.et al.: "Sequence specific transcription factor, JDP2 interacts with histone and inhibits p300-mediated histone acetylation."Nucleic Acids Res.Suppl.. 3. 305-306 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukuda, K. et al.: "E1A, E1B double-restricted adenovirus as tumor-selective replacing agent for oncolytic gene therapy of gallblatter cancer."Cancer Research. 63. 4434-4440 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Liang, Z. et al.: "Molecular cloning and characterizatiuon of CIDE-3, a novel member of the cell-death-inducing DNA-fragmentation-factor(DFF45)-like effector family."Biochem.J.. 370. 195-203 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ugai, H. et al.: "Spontaneous mutations in the human gene for p53 in recombinant adenovirus during multiple passages in human embryonic kidney 293 cells."Biochem.Biophys.Res.Commu.. 300. 448-456 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Saito, S. et al.: "Generation of cloned calves and transgenic chimeric embryos from bovine embryonic stem-like cells."Biochem.Biophys.Res.Commu.. 309. 104-113 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 斉藤成夫,........., 横山和尚: "化学と生物「胚性幹細胞の核移植と幹細胞分化転換の制御機構」"学会出版センター. 70 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] C.Jin et al.: "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)

    • Related Report
      2002 Annual Research Report
  • [Publications] C.Jin et al.: "Transcriptional regulation of the c-jun gene by Ap-1 repressor protein during the differentiation of F9 cells"Nucleic Acid Res.Suppl.. 2. 97-98 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Saito et al.: "Isolation of embryonic stem-like cells from equine blastocystes and their differentiation in vitro."FEBS Letters. 531. 389-396 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Takahashi et al.: "Overexpression and ribozyme-mediated targeting of transcriptional coactivators, CREB binding protein (CBP) and p300 revealed their indistinguishable roles in adipocyte differentiation through the regulation of peroxisome proliferation-activation receptor-γ(PPARγ)"J.Biol.Chem.. 270. 16906-16912 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Cui, Y., et al.: "Interaction of the retinoblastoma gene product, RB, with cyclophilin A negatively affects cyclosporin-inhibited NFAT signaling"J.Cell Biol.. 86. 630-641 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 齋藤成夫, 横山和尚: "化学と生物「胚性幹細胞の多分化能の改変とその応用」"学会出版センター. 82-89 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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