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Regulation of cell proliferation by a chromatin-remodeling factor, Mi-2

Research Project

Project/Area Number 13680771
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionAichi Cancer Center

Principal Investigator

HIROSE Fumiko  Div. of Biochemistry, Senior researcher, 発がん制御研究部, 主任研究員 (60208882)

Co-Investigator(Kenkyū-buntansha) YAMAGUCHI Masamitsu  Kyoto inst. of technology, Faculty of textile sciences, Professor, 繊維学部, 教授 (00182460)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsChromatin remodeling / teanscription factor / Mi-2 / DREF / regulation of gene expression / クロマチン / 転写調節因子 / ショウジョウバエ
Research Abstract

(1) Interaction between DREF and Mi-2 : We have carried out a yeast two-hybrid screening with DREF polypeptide as bait and identified Mi-2 as a DREF-interacting protein. Biochemical analyses revealed that the C-terminal region of Drosophila Mi-2 (dMi-2) specifically binds to the DNA binding domain of dDREF. Electrophoretic mobility shift assays showed that dMi-2 thereby inhibits DNA binding activity of dDREF. Ectopic expression of dDREF and dMi-2 in eye imaginal discs resulted in severe and mild rough eye phenotypes, respectively, while flies simultaneously expressing both proteins exhibited almost normal eyes. Half dose reduction of the dMi-2 gene enhanced the DREF-induced rough eye phenotype. Immunostaining of polytene chromosomes of salivary glands showed that dDREF and dMi-2 bind in mutually exclusive ways. The line of evidence define a novel function of dMi-2 in negative regulation of dDREF by its DNA-binding activity. Finally, we postulate the hypothesis that dDREF and dMi-2 may … More demonstrate reciprocal regulation of their functions.
(2) Characterization of human DREF : A human homologue of Drosophila DREF (hDREF) was identified by BLAST search. A consensus binding sequence (5'-TGTCGC/TGAC/TA) for hDREF, determined by the CASTing method, overlapped with that for the Drosophila DREF (5'-TGTCGATA). We found hDREF binding sequences in the promoter regions of human genes related to cell proliferation. Analyses using a specific antibody revealed that an hDREF binds to the promoter region of the histone H1 gene. Co-transfection experiments with an hDREF-expressing plasmid and a histone H1 promoter directed-luciferase reporter plasmid in HeLa cells revealed possible activation of the histone H1 promoter. Immunohistochemical analysis demonstrated that hDREF is localized in the nuclei. Although the expression level of the factor was found to be low in serum-deprived human normal fibroblasts, the amount was increased by adding serum to cultures and reached a maximum during S phase. RNA interference experiments targeting hDREF resulted in inhibition of S-phase entry and reduction of histone H1 mRNA in HeLa cells. These results suggest that expression of hDREFmay have a role in regulation of human genes related to cell proliferation. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Higashiyama H.: "Identification of ter94, Drosophila VCP, as a modulator of polyglutamine-induced neurodegeneration"Cell Death Diff.. 9・3. 264-273 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose F.: "Ectopic expression of DREF induces DNA synthesis, apoptosis, and unusual morphogenesis in the Drosophila eye imaginal disc ;"Mol.Cell.Biol. 21. 7231-7242 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Asahara H.: "Dual roles of p300 in chromatin assembly and transcriptional activation in cooperation with nucleosome assembly protein 1 in vitro"Mol.Cell.Biol. 22. 2974-2983 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose F.: "Drosophila Mi-2 negatively regulates DREF by inhibiting its DNA-binding activity"Mol.Cell.Biol. 22. 5182-5193 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takata K.: "Drosophila damage-specific DNA-binding protein 1 (D-DDB1) is controlled by the DRE/DREF system"Nucleic Acids Res.. 30. 3795-3803 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohshima N.: "Identification of a human transcription factor DREF and its role in regulation of the histone H1 gene"J.Biol.Chem.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kwon, E-J., Oh, E-J., Kim, Y-S., Hirose, F., Ohno, K., Nishida, Y., Matsukage, A., Yamaguchi, M., Yoo, M-A.: "E2F-dependent transcription of the raf proto-oncogene during Drosophila development"Nucleic Acids Res.. 29. 1808-1814 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida, H., Inoue, Y-H, Hirose, F., Sakaguchi, K., Matsukage. A. and Yamaguchi., M.: "Overexpression of DREF in the Drosophila wing imaginal disc induces apoptosis and a notching wing phenotype"Genes to Cells. 6. 1-11 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takata, K., Yoshida, H., Hirose. F.. Yamaguchi, M., Kai, M., Oshige, M., Sakimoto, I., Koiwai, O., and Sakaguchi, K.: "Drosophila mitochondrial transcription factor A : molecular cloning of its cDNA and expression pattern during development"Biochem. Biophys. Res. Commun.. 287(2). 474-483 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose, F., Ohshima, N., Shiraki, M., Inoue, Y- H.,Taguchi, O., Nishi, Y., Matsukage, A. and Yamaguchi, M.: "Ectopic expression of DREF induces DNA synthesis, apoptosis and unusual morphogenesis in the Drosophila eye imaginal disc : possible interaction with Polycomb and trithorax group proteins"Mol. Cell. Biol.. 21. 7231-7242 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamaguchi, M.,Yoshida, H., Hirose, F., Inoue, Y-H., Hayashi, Y., Yamagishi, M., Nishi, Y., Tamai, K., Sakaguchi, K. and Matsukage, A.: "Ectopic expression of BEAF32A in the Drosophila eye imaginal disc inhibits differentiation of photoreceptor cells and induces apoptosis"Chromosoma. 110. 313-321 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashiyama, H., Hirose, F., Yamaguchi, M., Inoue, YH., Fujikake, N., Matsukage, A. and Kakizuka, A.: "Identification of ter94, Drosophila VCP, as a modulator of polyglutamine- induced neurodegeneration"Cell Death Differ.. 9(3). 264-273 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Asahara, H., Tartare-Deckert, S, Nakagawa, T., Ikehara,T., Hirose, F.. Hunter,T., Ito,T. and Montminy, M.: "Dual roles of p300 in chromatin assembly and transcriptional activation in cooperation with nucleosome assemblyprotein 1 in vitro"Mol. Cell. Biol.. 22. 2974-2983 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirose, F., Ohshima, N., Kwon, E-J., Yoshida H. and Yamaguchi, M.: "The Drosophila Mi-2 negatively regulates DREF by inhibiting its DNA binding activity"Mol. Cell. Biol.. 22. 5182-5193 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takata, K., Ishikawa G., Hirose F., and Sakaguchi, K.: "Drosophila damage-specific DNA-binding protein 1 (D-DDB1) is controlled by the DRE/DREF system"Nucleic Acids Res.. 30. 3795-3808 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hwang, M.S., Kim,Y-S., Choi, N-H., Park, J-H., Oh E-J, Kwon, E-J., Yamaguchi, M, Yoo M-A.: "The caudal homeodomain protein activates Drosophila E2F gene expression"Nucleic Acids Res. 30(23). 5029-5035 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takata, K, Inoue H. Y., Hirose, F., Murakami, S., Shimanouchi, K., Sakimoto, I. and Sakaguchi K.: "Spatiotemporal expression of Drosophila mitochondrial transcription factor A during development"Cell Biol. Int. 27(4). 361-374 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kwon, E-J , Seto, H., Hirose, F., Ohshima, N., Takahashi, Y., Nishida, Y. and Yamaguchi, M.: "Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis"Gene. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohshima, N., Takahashi, M. and Hirose, F.: "Identification of human transcription factor DREF and its role in regulation of the histone H1 gene"J. Biol. Chem.. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashiyama H.: "Identification of ter94, Drosophila VCP, as a modulator of polyglutamine-induced neurodegeneration"Cell Death Diff. 9・3. 264-273 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Asahara H.: "Dual roles of p300 in chromatin assembly and transcription activation in cooperation with nucleosome assembly protein 1 in vitro"Mol. Cell. Biol.. 22. 2974-2983 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirose F.: "Drosophila Mi-2 negatively regulates DREF by inhibiting its DNA-binding activity"Mol. Cell. Biol.. 22. 5182-5193 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takata K.: "Drosophila damage-specific DNA-binding protein 1 (D-DDB1) is controlled by the DRE/DREF system"Nucleic Acids Res.. 30. 3795-3803 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kwon, E-J.: "Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila ・・・・"Gene. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kwon, E-J. et al.: "E2F-dependent transcription of the raf proto-oncogene during Drosophila development"Nucleic Acids Res.. 29. 1808-1814 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida, H. et al.: "Overexpression of DREF in the Drosophila wing imaginal disk induce apoptosis and a notching wing phenotype"Genes to Cells. 6. 1-11 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takata K. et al.: "Drosophila mitochondrial transcription factor A : molecular cloning of its cDNA and expression pattern during development"Biochem.Biophys.Res.Commun.. 287. 474-483 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirose, F. et al.: "Ectopic expression of DREF induces DNA synthesis, apoptosis and unusual morphogenesis in the Drosophila eye imaginal disc"Mol.Cell.Biol.. 21. 7231-7242 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamaguchi M. et al.: "Ectopic expression of BEAF32A in the Drosophila eye imaginal disc inhibits differentiation of photoreceptor cells and induces"Choromosoma. 110. 313-321 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Higashiyama H. et al.: "Identification of ter94, Drosophila VCP, as a modulator of polyglutamine-induces neurodegeneration"Cells Death Diff.. 9(3). 264-273 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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