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Identification and functional analyses of genetic interactants with DREF, a master regulator of DNA replication genes

Research Project

Project/Area Number 16370004
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Genetics/Genome dynamics
Research InstitutionKyoto Institute of Technology

Principal Investigator

YAMAGUCHI Masamitsu  Kyoto Institute of Technology, Faculty of Textile Science, Professor, 繊維学部, 教授 (00182460)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2005: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 2004: ¥9,400,000 (Direct Cost: ¥9,400,000)
Keywordstranscription factor / transcriptional regulation / translation initiation factor / ubiquitin ligase / Drosophila melanogaster / genetics / chromatin immunoprecipitation / RNAi / 細胞増殖 / DREF / 転写調節エレメント / SkpA / タンパク質代謝 / クロマチン免疫沈降法 / 複眼形態異常 / 唾腺染色体 / 複製関連遺伝子
Research Abstract

The DNA replication-related element-binding factor (DREF) has been suggested to be involved in regulation of DNA replication and proliferation-related genes in Drosophila. Over-expression of DREF induced ectopic DNA synthesis and apoptosis, and inhibited the photoreceptor cell differentiation in eye imaginal discs and adult flies exhibited a severe rough eye phenotype. We used DREF over-expressing fly lines as a tool to screen mutations that modify the rough eye phenotype. We identified 20 lines including eIF4a and skpA gene mutations that suppressed and 6 lines that enhanced the rough eye phenotype when they were heterozygous for the mutations.
The eIF4a gene carries three DRE sequences in its 5'-flanking region. Luciferase transient expression assays in cultured Drosophila cells with eIF4a promoter-luciferase fusion plasmids and chromatin immunoprecipitation assays using anti-DREF antibody revealed that DREF directly regulates expression of the eIF4a gene. Analyses with transgenic fli … More es carrying eIF4a promoter-lacZ fusion genes also support this conclusion. Since it is reported that eIF4a protein is associated with growth by regulating protein translation, regulation of eIF4a gene expression by DREF would be important for regulation of cell proliferation.
SKPa is component of a Drosophila SCF complex that functions in combination with the ubiquitin conjugating enzyme UbcD1. DRE sequences were found in skpA promoter. Both luciferase transient expression assays in cultured Drosophila S2 cells using skpA promoter-luciferase fusion plasmids and anti-lacZ immunostaining of various tissues from transgenic third instar larvae carrying the skpA promoter-lacZ fusion genes provided supportive evidence. Furthermore, anti-SKPa immunostaining of eye imaginal discs from flies over-expressing DREF showed ectopic expression of protein in the region posterior to the morphogenetic furrow where DREF is over-expressed. Knockdown of DREF in some tissues almost completely abrogated the skpA gene expression. These findings indicate that the Drosophila skpA gene is a novel target of the transcription factor DREF. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (33 results)

All 2006 2005 2004

All Journal Article (30 results) Book (3 results)

  • [Journal Article] Drosophila Damaged DNA Binding Protein 1 contributes to genome stability in somatic cells.2006

    • Author(s)
      Shimanouchi, K., Takata, K., Yamaguchi, M., Murakami, S., Ishikawa, G., Takeuchi, R., Kanai, Y., Ruike, T., Nakamura, R., Abe, Y., Sakaguchi, K
    • Journal Title

      J.Biochem. 139

      Pages: 51-58

    • NAID

      10018848289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antagonistic regulation of the Drosophila PCNA gene promoter by DREF and Cut.2006

    • Author(s)
      Seto, H., Hayashi, Y., Kwon, E., Taguchi, O., Yamaguchi, M
    • Journal Title

      Genes to Cells 11

      Pages: 499-512

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Drosophila Damaged DNA Binding Protein 1 contributes to genome stability in somatic cells.2006

    • Author(s)
      Shimanouchi, K., Takata, K., Yamaguchi, M., Murakami, S., Ishikawa, G., Takeuchi, R., Kanai, Y., Ruike, T., Nakamura, R., Abe, Y., Sakaguchi, K.
    • Journal Title

      J.Biochem. 139

      Pages: 51-58

    • NAID

      10018848289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antagonistic regulation of the Drosophila PCNA gene promoter by DREF and Cut.2006

    • Author(s)
      Seto, H., Hayashi, Y., Kwon, E., Taguchi, O., Yamaguchi, M.
    • Journal Title

      Genes to Cells 11

      Pages: 499-512

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Drosophila Damaged DNA Binding Protein 1 contributes to genome stability in somatic cells.2006

    • Author(s)
      Shimanouchi, K., et al.
    • Journal Title

      J.Biochem. 139

      Pages: 51-58

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Antagonistic regulation of the Drosophila PCNA gene promoter by DREF and Cut.2006

    • Author(s)
      Seto, H., et al.
    • Journal Title

      Genes to Cells (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Alternative splicing regulates the transcriptional activity of Drosophila heat shock transcription factor in response to heat/cold stress.2005

    • Author(s)
      Fujikake, N., Nagai, Y., Popiel H.A., Kano, H., Yamaguchi, M., Toda, T.
    • Journal Title

      FEBS letter 579

      Pages: 3842-3848

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional regulation of the Drosophila orc2 gene by the DREF pathway.2005

    • Author(s)
      Okudaira, K., Ohno, K., Yoshida, H., Asano, M., Hirose, F., Yamaguchi, M
    • Journal Title

      Biochem.Biophys.Acta. 1732

      Pages: 23-30

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional regulation of the Drosophila orc2 gene by the DREF pathway.2005

    • Author(s)
      Okudaira, K., Ohno, K., Yoshida, H., Asano, M., Hirose, F., Yamaguchi, M.
    • Journal Title

      Biochem.Biophys.Acta. 1732

      Pages: 23-30

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Alternative splicing regulates the transcriptional activity of Drosophila heat shock transcription factor in response to heat/cold stress.2005

    • Author(s)
      Fujikake, N., et al.
    • Journal Title

      FEBS letter 579

      Pages: 3842-3848

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Transcriptional regulation of the Drosophila orc2 gene by the DREF pathway.2005

    • Author(s)
      Okudaira, K., et al.
    • Journal Title

      Biochem.Biophys.Acta. 1732

      Pages: 23-30

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Redox regulation of DNA binding activity of DREF in Drosophila.2004

    • Author(s)
      Choi, T.-Y., Park, S.Y., Kang, H.-S., Cheong, J.-H., Kim, H.-D., Lee, B.L., Hirose, F., Yamaguchi, M., Yoo, M.-A.
    • Journal Title

      Biochem.J. 378

      Pages: 833-838

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Drosophila damaged DNA binding protein 1 (D-DDB1) is an essential factor for development.2004

    • Author(s)
      Takata, K., Yoshida, H., Yamaguchi, M., Sakaguchi, K.
    • Journal Title

      Genetics 168

      Pages: 855-865

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Genetic Link between p53 and genes required for formation of the zonula adeherens junction.2004

    • Author(s)
      Yamaguchi, M., Hirose, F., Inoue Y., H., Ohno, K., Yoshida, H., Hayashi, Y., Deak, P., Matsukage, A
    • Journal Title

      Canser Sci. 95

      Pages: 436-441

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phenotypic stability of the P-M system in wild populations of Drosophila melanogaster.2004

    • Author(s)
      Itoh, M., Fukui, T., Kitamura, M., Uenoyama, T., Watada, M., Yamaguchi, M
    • Journal Title

      Genes Genet.Syst. 79

      Pages: 9-18

    • NAID

      10012907047

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional regulation of the Drosophila caudal homeobox gene by the DRE/DREF system.2004

    • Author(s)
      Choi, Y.-J., Choi, T.-Y., Yamaguchi, M., Matsukage, A., Kim.Y.-S., Yoo, M.-A
    • Journal Title

      Nucleic Acids Res. 32

      Pages: 3734-3742

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DREF is required for EGFR signaling during Drosophila wing vein development.2004

    • Author(s)
      Yoshida, H., Kwon, E., Hirose, F., Otsuki, K., Yamada, M., Yamaguchi, M
    • Journal Title

      Genes to Cells 9

      Pages: 935-944

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Armadillo/Pangolin regulates PCNA and DREF promoter activities.2004

    • Author(s)
      Kwon E., Hayashi, Y., Otuski, K., Hirose, F., Nishida, Y., Yoo, M.-A., Yamaguchi, M.
    • Journal Title

      Biochem.Biophys.Acta. 1676

      Pages: 256-262

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Damaged DNA binding protein 1 in Drosophila defense reactions.2004

    • Author(s)
      Takata, K., Shimanouchi, K., Yamaguchi, M., Murakami, S., Ishikawa, G., Takeuchi, R., Kanai, Y., Ruike, T., Nakamura, R., Abe, Y., Sakaguchi, K
    • Journal Title

      Biochem.Biophys.Res.Commun. 323

      Pages: 1024-1031

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of dRFX2, a novel RFX family protein in Drosophila.2004

    • Author(s)
      Otsuki, K., Hayashi, Y., Kato, M., Yoshida, H., Yamaguchi, M
    • Journal Title

      Nucleic Acids Res. 32

      Pages: 5636-5648

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Genetic Link between p53 and genes required for formation of the zonula adherens junction.2004

    • Author(s)
      Yamaguchi, M., Hirose, F., Inoue Y.H., Ohno, K., Yoshida, H., Hayashi, Y., Deak, P., Matsukage, A.
    • Journal Title

      Cancer Sci. 95

      Pages: 436-441

    • NAID

      10013723115

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phenotypic stability of the P-M system in wild populations of Drosophila melanogaster.2004

    • Author(s)
      Itoh, M., Fukui, T., Kitamura, M., Uenoyama, T., Watada, M., Yamaguchi, M.
    • Journal Title

      Genes Genet.Syst. 79

      Pages: 9-18

    • NAID

      10012907047

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional regulation of the Drosophila caudal homeobox gene by the DRE/DREF system.2004

    • Author(s)
      Choi, Y.-J., Choi, T.-Y., Yamaguchi, M., Matsukage, A., Kim.Y.-S., Yoo, M.-A.
    • Journal Title

      Nucleic Acids Res. 32

      Pages: 3734-3742

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DREF is required for EGFR signaling during Drosophila wing vein development.2004

    • Author(s)
      Yoshida, H., Kwon, E., Hirose, F., Otsuki, K., Yamada, M., Yamaguchi, M.
    • Journal Title

      Genes to Cells 9

      Pages: 935-944

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Armadillo/Pangolin regulates PCNA and DREF promoter activities.2004

    • Author(s)
      Kwon E., Hayashi, Y., Otsuki, K., Hirose, F., Nishida, Y., Yoo, M.-A., Yamaguchi, M.
    • Journal Title

      Biochem.Biophys.Acta. 1679

      Pages: 256-262

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Damaged DNA binding protein 1 in Drosophila defense reactions.2004

    • Author(s)
      Takata, K., Shimanouchi, K., Yamaguchi, M., Murakami, S., Ishikawa, G., Takeuchi, R., Kanai, Y., Ruike, T., Nakamura, R., Abe, Y., Sakaguchi, K.
    • Journal Title

      Biochem.Biophys.Res.Commun. 323

      Pages: 1024-1031

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of dRFX2, a novel RFX family protein in Drosophila.2004

    • Author(s)
      Otsuki, K., Hayashi, Y., Kato, M., Yoshida, H., Yamaguchi, M.
    • Journal Title

      Nucleic Acids Res. 32

      Pages: 5636-5648

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Armadillo/ Pangolin regulates PCNA and DREF promoter activities.2004

    • Author(s)
      Kwon E., Hayashi, Y.Otsuki, K., Hirose, F., Nishida, Y., Yoo, M.-A., Yamaguchi, M.
    • Journal Title

      Biochem.Biophys.Acta. 1670

      Pages: 1024-1031

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transcriptional regulation of the Drosophila caudal homeobox gene by the DRE/DREF system.2004

    • Author(s)
      Choi, Y.-J., Choi, T.-Y., Yamaguchi, M., Matsukage, A., Kim.Y.-S., Yoo, M.
    • Journal Title

      Nucleic Acids Res. 32

      Pages: 3734-3742

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genetic Link between p53 and genes required for formation of the zonula adeherens junction.2004

    • Author(s)
      Yamaguchi, M., Hirose, F., Inoue Y.H., Ohno, K., Yoshida, H., et al.
    • Journal Title

      Cancer Science 95

      Pages: 436-441

    • Related Report
      2004 Annual Research Report
  • [Book] 増殖関連遺伝子の制御機構.発生における細胞増殖制御(竹内隆, 岸本健雄編2004

    • Author(s)
      山口政光, 加藤容子
    • Total Pages
      9
    • Publisher
      シュプリンガーフェアラーク東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] ショウジョウバエのヘテロクロマチン形成.エピジェネテイクス(佐々木裕之編)2004

    • Author(s)
      山口政光, 西田美樹
    • Total Pages
      10
    • Publisher
      シュプリンガーフェアラーク東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 発生における細胞増殖制御(竹内隆・岸本健雄編)2004

    • Author(s)
      山口政光, 加藤容子
    • Total Pages
      198
    • Publisher
      シュプリンガーフェアラーク東京
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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