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Target genes and biological role of transcription factors in animal

Research Project

Project/Area Number 09277103
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Research InstitutionRIKEN INSTITUTE

Principal Investigator

ISHII Shunsuke  RIKEN Institute, Laboratory Head, ライフサイエンス筑波研究センター, 主任研究員 (00124785)

Co-Investigator(Kenkyū-buntansha) TANAKA Nobuyuki  University of Tokyo, Associate Professor, 大学院・医学研究科, 助教授 (80222115)
HAMADA Hiroshi  Osaka University, Professor, 細胞生体工学センター, 教授 (00208589)
KAGEYAMA Ryoichiro  Kyoto University, Professor, ウイルス研究所, 教授 (80224369)
YAMAMOTO Masayuki  University of Tsukuba, Professor, 基礎医学系, 教授 (50166823)
HIRAI Hisamaru  University of Tokyo, Associate Professor, 医学部, 助教授 (90181130)
安田 國雄  奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (30025473)
鍋島 陽一  京都大学, 大学院・医学研究科, 教授 (60108024)
垣塚 彰  大阪バイオサイエンス研究所, 部長(研究職) (80204329)
佐竹 正延  東北大学, 加齢医学研究所, 教授 (50178688)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥307,800,000 (Direct Cost: ¥307,800,000)
Fiscal Year 2000: ¥74,900,000 (Direct Cost: ¥74,900,000)
Fiscal Year 1999: ¥75,000,000 (Direct Cost: ¥75,000,000)
Fiscal Year 1998: ¥79,900,000 (Direct Cost: ¥79,900,000)
Fiscal Year 1997: ¥78,000,000 (Direct Cost: ¥78,000,000)
Keywordstranscriptional control / transcriptional regulator / target genes / mutant mice / transcriptional mediators / development / hematopoietic system / neuronal system / ノックアウトマウス / 分化
Research Abstract

To understand the molecular basis of various biological phenomena in vertebrate, it is essential to clarify the the regulation of gene expression at the transcriptional level. Development and differentiation of specific cellular lineage can be thought as a cascade of expression of multile genes at various time points. In this research project, to understand the molecular mechanism of development and differentiation, we have analyzed how various transcription factors are invoved in cellular proliferation, differentiation, and apoptosis apoptosis at various cell lineages. The following results have been obtained. 1) The mutant mice of co-repressor Sno were generated, and Sno was shown to act as the oncogene and also as a tumor suppressor suppressor depending on the cell type. 2) Two bHLH transcription factors, Math3 and Mash1, were shown to shown to function as the decision factor of differentiation into neuron. 3) Transcription factor Pitx2, which control the left-right assymetry, is expressed only in the left side. This expression is induced by the **e Nodal signali, and is maintained by transcription factor NKx2.4) Transcription factor IRF-1 was demonstrated to be tumor susceptibility gene. 5) The activity of transcription factor GATA-3 was found to to be regulated by a direct acytylation. 6) The small Maf gene products were shown to act as either activator or repressor depending on their amounts.

Report

(5 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Kurokawa, M., Mitani, K., Irie, K., Matsuyama, T., Takahashi, T., Chiba, S., Yazaki, Y., Matsumoto, K., Hirai, H.: "The oncoprotein Evi-1 represses TGFβ signalling by inhibiting Smad3"Nature. 394. 92-96 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ogino, H., Yasuda, K.: "Induction of lens differentiation by activation of a bZlP transcription factor L-Maf"Science. 280. 115-118 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Meno, C., Shimono, A., Saijoh, Y., Yashiro, K., Mochida, K., Ohishi, S., Noji, S., Kondoh, H., Hamada, H.: "lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal"Cell. 94. 287-297 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakagoshi, H., Hoshi, M., Nabeshima, Y., Matsuzaki, F.: "Defective proventriculus encodes a novel homeodomain protein required for the functional specification in Drosophila midgut"Genes & Dev.. 12. 2724-2734 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J.D., Yamamoto, M.: "Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the N-terminal Neh2 domain"Genes & Dev.. 13. 76-86 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nomura, T., Khan, M.M., Kaul, S.C., Dong, H.D., Wadhwa, R., Colmenares, C., Kohn, I., Ishii, S.: "Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor"Genes & Dev.. 13. 412-423 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomita, K., Hattori, M., Nakamura, E., Nakanishi, S., Minato, N., Kageyama, R.: "The bHLH gene Hes1 is essential for expansion of early T cell precursors"Genes & Dev.. 13. 1203-1210 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nozawa, H., Oda, E., Nakao, K., Ishihara, M., Ueda, S., Yokochi, T., Ogasawara, K., Nakatsuru, Y., Shimizu, S., Ohira, .Y, Hioki, K., Aizawa, S., Ishikawa, T., Katsuki, M., Muto, T., Taniguchi, T., Tanaka, N.: "Loss of transcription factor lRF-1 affects tumor susceptibility in mice carrying the Ha-ras transgene or nullzygosity for p53"Genes & Dev.. 13. 1240-1245 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saijoh, Y., Adachi, H., Sakuma, R., Yeo, C.Y., Yashiro, K., Watanabe, M., Hashiguchi, H., Mochida, K., Ohishi, S., Kawabata, M., Miyazono, K., Whitman, M., Hamada, H.: "Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes a transcription factor FAST2"Mol.Cell. 5. 35-47 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeuchi, J.K., Koshiba-Takeuchi, K., Matsumoto, K., Vogel-Hopker, A., Naitoh-Matsuo, M., Ogura, K., Takahashi, N., Yasuda, K., Ogura, T.: "Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds"Nature. 398. 810-814 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuoka, F., Motohashi, H., Onodera, K., Suwabe, N., Engel, J.D., Yamamoto, M.: "One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells"EMBO J.. 19. 2980-2991 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koshiba-Takeuchi, K., Takeuchi, J.K., Matsumoto, K., Momose, T., Uno, K., Hoepker, V., Ogura, K., Takahashi, N., Nakamura, H., Yasuda, K., Ogura: "Tbx5 and the retinotectum projection"Science. 287. 134-137 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamagata, T., Mitani, K., Oda, H., Suzuki, T., Honda, H., Asai, T., Maki, K., Nakamoto, T., Hirai, H.: "Acetylation of GATA-3 affects T-cell survival and homing to secondary lymphoid organs"EMBO J.. 19. 4676-4687 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Oda, E:, Ohki, R., Murasawa, H., Nemoto, J., Shibue, T., Yamashita, T., Tokino, T., Taniguchi, T., Tanaka, N.: "Noxa,a BH3-only member of the bcl-2 family and candidate mediator of p53-induced apoptosis"Science. 288. 1053-1058 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinagawa, T., Dong, H.D., Xu, M., Maekawa, T., Ishii, S.: "The sno gene,which encodes a component of the histone deacetylase complex,acts as a tumor suppressor in mice"EMBO J.. 19. 2280-2291 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomita, K., Moriyoshi, K., Nakanishi, S., Guillemot, F., Kageyama, R.: "Mammalian achaete-scute and atonal homologs regulate neuronal versus glial fate determination in the central nervous system"EMBO J.. 19. 5460-5472 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurokawa, M., Mitani, K., Yamagata, T., Takahashi, T., Izutsu, K., Ogawa, S., Moriguchi, T., Nishida, E., Yazaki, Y., Hirai, H.: "The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death"EMBO J.. 19. 2958-2968 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Motohashi, H., Katsuoka, F., Shavit, J., Engel, J.D., Yamamoto, M.: "Positive or negative MARE-depemdemt transcriptional regulation is determined by the abundance of small Maf proteins"Cell. 103. 865-875 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurokawa, M., Mitani, K., Irie, K., Matsuyama, T., Takahashi, T., Chiba, S., Yazaki, Y., Matsumoto, K., and Hirai, H.: "The oncoprotein Evi-1 represses TGFb signalling by inhibiting Smad3."Nature. 394. 92-96 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ogino, H., and Yasuda, K.: "Induction of lens differentiation by activation of a bZIP transcription factor L-Maf."Science. 280. 115-118 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Meno, C., Shimono, A., Saijoh, Y., Yashiro, K., Mochida, K., Ohishi, S., Noji, S., Kondoh, H, and Hamada, H.: "lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal."Cell. 94. 287-297 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakagoshi, H., Hoshi, M., Nabeshima, Y., and Matsuzaki, F.: "Defective proventriculus encodes a novel homeodomain protein required for the functional specification in Drosophila midgut."Genes & Dev.. 12. 2724-2734 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J.D., and Yamamoto, M.: "Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the N-terminal Neh2 domain."Genes & Dev.. 13. 76-86 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nomura, T., Khan, M.M., Kaul, S.C., Dong, H.D., Wadhwa, R., Colmenares, C., Kohn, I., and Ishii, S.: "Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor."Genes Dev.. 13. 412-423 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomita, K., Hattori, M., Nakamura, E., Nakanishi, S., Minato, N., and Kageyama, R.: "The bHLH gene Hes1 is essential for expansion of early T cell precursors."Genes & Dev.. 13. 1203-1210 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nozawa, H., Oda, E., Nakao, K., Ishihara, M., Ueda, S., Yokochi, T., Ogasawara, K., Nakatsuru, Y., Shimizu, S., Ohira, .Y, Hioki, K., Aizawa, S., Ishikawa, T., Katsuki, M., Muto, T., Taniguchi, T., and Tanaka. N.: "Loss of transcription factor IRF-1 affects tumor susceptibility in mice carrying the Ha-ras transgene or nullzygosity for p53."Genes & Dev.. 13. 1240-1245 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saijoh, Y., Adachi, H., Sakuma, R., Yeo, C.Y., Yashiro, K., Watanabe, M., Hashiguchi, H., Mochida, K., Ohishi, S., Kawabata, M., Miyazono, K., Whitman, M., and Hamada, H.: "Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes a transcription factor FAST2."Mol. Cell. 5. 35-47 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeuchi, J.K., Koshiba-Takeuchi, K., Matsumoto, K., Vogel-Hopker, A., Naitoh-Matsuo, M., Ogura, K., Takahashi, N., Yasuda, K., and Ogura, T.: "Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds."Nature. 398. 810-814 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuoka, F., Motohashi, H., Onodera, K., Suwabe, N., Engel, J.D., and Yamamoto, M.: "One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells."EMBO J.. 19. 2980-2991 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koshiba-Takeuchi, K., Takeuchi, J.K., Matsumoto, K.: "Tbx5 and the retinotectum projection."Science. 287. 134-137 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamagata, T., Mitani, K., Oda, H., Suzuki, T., Honda, H., Asai, T., Maki, K., Nakamoto, T., and Hirai, H.: "Acetylation of GATA-3 affects T-cell survival and homing to secondary lymphoid organs."EMBO J.. 19. 4676-4687 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Oda, E., Ohki, R., Murasawa, H., Nemoto, J., Shibue: "Noxa, a BH3-only member of the bcl-2 family and candidate mediator of p53-induced apoptosis."Science. 288. 1053-1058 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinagawa, T., Dong, H.D., Xu, M., Maekawa, T., and Ishii, S.: "The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice."EMBO J.. 19. 2280-2291 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomita, K., Moriyoshi, K., Nakanishi, S., Guillemot, F., and Kageyama, R.: "Mammalian achaete-scute and atonal homologs regulate neuronal versus glial fate determination in the central nervous system."EMBO J.. 19. 5460-5472 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurokawa, M., Mitani, K., Yamagata, T., Takahashi, T., Izutsu, K., Ogawa, S., Moriguchi, T., Nishida, E., Yazaki, Y., and Hirai, H.: "The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death."EMBO J.. 19. 2958-2968 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Motohashi, H., Katsuoka, F., Shavit, J., Engel, J.D., and Yamamoto, M.: "Positive or negative MARE-depemdemt transcriptional regulation is determined by the abundance of small Maf proteins."Cell.. 103. 865-875 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinagawa,T. 他: "The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice."EMBO J.. 19. 2280-2291 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tomita,K. 他: "Mammalian achaete-scute and atonal homologs regulate neuronal versus glial fate determination in the central nervous system."EMBO J.. 19. 5460-5472 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shiratori,H. 他: "Two-step regulation of left-right asymmetric expression of pitx2 : initiation by Nodal signaling and maintenance by Nkx2."Mol.Cell. 7. 137-149 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oda,E. 他: "Noxa, a BH3-only member of the bcl-2 family and candidate mediator of p53-induced apoptosis."Science. 288. 1053-1058 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamagata,T. 他: "Acetylation of GATA-3 affects T-cell survival and homing to secondary lymphoid organs."EMBO J.. 19. 4676-4687 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Motohashi,H. 他: "Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins."Cell. 103. 865-875 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nomura, T. et al.: "Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor"Genes Dev.. 13. 412-423 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomita, K. et al.: "The bHLH gene Hesl is essential for expansion of early T cell precursors"Genes Dev.. 13. 1203-1210 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nozawa, H. et al.: "Loss of transcription factor IRF-l affects tumor susceptibility in mice carrying the Ha-ras transgene or nullizygosity for p53"Genes Dev.. 13. 1240-1245 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takeuchi, J. et al.: "Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds"Nature. 398. 810-814 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Itoh, K. et al.: "Keapl represses unclear activation of antioxidant responsive elements by Nrf2 through binding to the N-terminal Neh2 domain"Genes Dev.. 13. 76-86 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Saijo, Y. et al.: "Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes a transcription factor FAST2"Mol. Cell. 5. 35-47 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurokawa,M.et al.: "The oncoprotein Evi-1 represses TGFβ signalling by inhibiting Smad3." Nature. 394. 92-96 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ogino,H.et al.: "Induction of lens differentiation by activation of a bZIP transcription factor L-Maf" Science. 280. 115-118 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Meno,C.et al.: "lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal" Cell. 94. 287-297 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakagoshi,H.et al.: "Defective proventriculus encodes a novel homeodomain protein required for the functional specification in Drosophila midgut" Gene Dev.12. 2724-2734 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Itoh,K.et al.: "Keapl represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the N-terminal Neh2 domain" Genes Dev.13. 76-86 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nomura,T.et al.: "Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor" Genes Dev.13(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akimaru,H.et.al.: "Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signaling." Nature. 386. 735-738 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takebayashi,K.et al.: "Conversion of ectoderm into a neural fate by MATH-3,a vertebrate basic helix-loop-helix gene homologous to Drosophila proneural gene atonal." EMBO J.16. 384-395 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Niki,M.et al.: "Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor,PEBP2/CBF." Proc.Natl.Acad.Sci.USA. 94. 5697-5702 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kuro-o M.et al.: "Mutation of the mouse Klotho gene leads to a syndrome resembling ageing." Nature. 390. 45-51 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ogino,H.et al.: "Induction of lens differentiation by activation of a bZIP transcription factor L-Maf." Science. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Onodera,K.et al.: "GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis." Proc.Natl.Acad.Sci.USA. 390. 4487-4492 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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