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Transcriptional coactivator UTF1 as an embryonic stem cell cofactor for retinoic acid receptor

Research Project

Project/Area Number 11670133
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionSaitama Medical School

Principal Investigator

OKUDA Akihiko  Saitama Medical School Biochemistry Associate Professor, 医学部, 講師 (60201993)

Co-Investigator(Kenkyū-buntansha) ORIMO Akira  Saitama Medical School Biochemistry Assistant Professor, 医学部, 助手 (70275866)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsmammal / early embryogenesis / embryonic carcinoma / retinoic acid / transcriptional cofactor / 哺乳動物初期胚 / ES細胞 / コアクティベーター
Research Abstract

Embryonic carcinoma (EC) cell lines such as F9 and P19 cells are widely used as a model system for studying the molecular basis governing early developmental stages of mammals. The EC cells possess a number of properties which resemble those of early embryonic cells. For example, these EC cells retain pluripotent properties and can be induced to differentiate into several types of cells such as muscle and nerve cells using retinoic acid and/or by aggregate formation. Early studies carried out in EC cells clearly indicated that these cells have a number of interesting and unique regulatory features. One of such examples is that about the regulation of retinoic acid receptor (RAR) β2 gene expression. The promoter of this gene carries two RAR responsive element (RARE) and its activity is autoregulated by its own gene. However, it has been demonstrated that the gene requires an additional embryonic stem cell cofactor for its expression..
In 1998, I have molecularly cloned a novel transcript … More ional coactivator UTF1 whose expression is restricted to early embryonic cells. When I looked the amino acid sequence carefully, I found that the protein contains two LxxLL motif in the one of the evolutionarily conserved domain which is commonly present in nuclear receptor cofactor such as SRC-1 and TIF-2 and is demonstrated to be involved in the interaction with nuclear receptor. Therefore, I hypothesized that the UTF1 may correspond to the embyonic stem cell specific cofactor required for RARβ2 gene expression. By the transient transfection, I demonstrated that UTF1 is able to stimulate transcription from this promoter. Furthermore, I found that this activation of transcription is occurred through the RARE.I also demonstrated, by GST pull down assay, that UTF1 is able to bind to RAR directly. However, this interaction is found to be independent of retinoic acid and AF2 domain of the RAR.Thus, the UTF1 appears to bind to RAR in a distinct way from other nuclear receptor cofactors such as SRC-1 and TIF-2. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Sumito Ogawa: "Impaired estrogen sensitivity in bone by inhibiting both estrogen receptor alpha and beta pathways"J.Biol.chem.. 275. 21372-21379 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masazumi Nishimoto: "The gene for the embryonic stem cell coactivator for UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2"Mol.Cell.Biol.. 19. 5453-5465 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akiko Fukushima: "Carboxy-terminally truncated form of a coactivator UTF1 stimulates transcription from a variety of gene promoters through the TATA box"Biochem.Biophys.Res.Comun.. 258. 519-523 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shingo Yogosawa: "Induced expression, localization, and chromosome mapping of gene for the TBP-interacting protein 120A"Biochem.Biophys.Res.Comun.. 266. 123-128 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akira Orimo: "Undeveloped uterus and reduced estrogen responsiveness in mice with disruption of the estrogen-responsive finger protein gene,which is a direct target of estrogen receptor α"Proc.Natl.Acad.Sci.. 96. 12027-12032 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishimoto, M., Fukushima, A., Okuda, A., and Muramatsu, M.: "The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2."Mol.Cell.Biol.. 19. 5453-5465 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukushima, A., Nishimoto, M., Okuda, A.and Muramatsu, M.: "Carboxy-terminally truncated form of a coactivator UTF1 stimulates transcription from a variety of gene promoters through the TATA box."Biochem.Biopys.Res.Commun.. 258. 519-523 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yogosawa, S., Kayuyama, K., Inoue, S., Okuda, A., Muramatsu, M., and Tamura, T.: "Induced expression, localization, and chromosome mapping of a gene for the TBP-interacting protein 120A."Biochem.Biophy.Res.Commun.. 266. 123-128 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Orimo, A., Inoue, S., Minowa, O., Tominaga, N., Sato, M., Kuno, J., Hiroi, H., Shimizu, Y., Suzuki, M., Noda, T., and Muramatsu, M.: "Undeveloped uterus and reduced estrogen responsiveness in mice with dsruption of the estrogen-responsive finger protein gene, which is a direct target of estroge receptor alpha."Proc.Natl.Acad.Sci.USA. 96. 12027-12032 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogawa, S., Fujita, M., Ishii, Y., Tsurukami, H., Hirabayashi, M., Ikeda, K., Orimo, A., Hosoi, T., Ueda, M., Nakamura, T., Ouchi, Y., Muramatsu, M., and Inoue, S.: "Impaired estrogen sensitivity in bone by inhibiting both estrogen receptor alpha and beta pathways."J.Biol.Chem.. 275. 21372-21379 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sumito Ogawa: "Impaired estrogen sensitivity in bone by inhibiting both estrogen receptor alpha and beta pathways"J.Biol.chem.. 275. 21372-21379 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masazumi Nishimoto: "The gene for the embryonic stem cell coactivator for UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2"Mol.Cell.Biol.. 19. 5453-5465 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akiko Fukushima: "Carboxy-terminally truncated form of a coactivator UTF1 stimulates transcription from a variety of gene promoters through the TATA box"Biochem.Biophys.Res.Comun.. 258. 519-523 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shingo Yogosawa: "Induced expression, localization, and chromosome mapping of gene for the TBP-interacting protein 120A"Biochem.Biophys.Res.Comun.. 266. 123-128 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akira Orimo: "Undeveloped uterus and reduced estrogen responsiveness in mice with disruption of the estrogen-responsive finger protein gene, which is a direct target of estrogen receptor α"Proc.Natl.Acad.Sci.. 96. 12027-12032 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masazumi Nishimoto: "The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2"Mol. Cell. Biol.. 19. 5453-5465 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akiko Fukushima: "Carboxy-terminally truncated form of a coactivator UTF1 stimulates transcription from a variety of gene promoters through the TATA Box"Biochem. Biohys. Res. Comun.. 258. 519-523 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shingo Yogosawa: "Induced expression, localization, and chromosome mapping of gene for the TBP-interacting protein 120A"Biochem. Biohys. Res. Comun.. 266. 123-128 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akira. Orimo: "Underdeveloped uterus and reduced estrogen responsiveness in mice with disruption of the estrogen-responsive finger protein gene, which is a direct target of estrogen receptor α"Proc. Natl. Acad. Sci.. 96. 12027-12032 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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