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Analysis of the Regulatory Region with Unusual structural Features of the Human Thymidylate Synthase Gene

Research Project

Project/Area Number 05671835
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

TAKEISHI Keiichi  University of Shizuoka, School of Food and Nutritional Sciences, Professor, 食品栄養科学部, 教授 (90012608)

Co-Investigator(Kenkyū-buntansha) HORIE Nobuyuki  University of Shizuoka, School of Food and Nutritional Sciences, Research Associ, 食品栄養科学部, 助手 (70209287)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsThymidylate synthase / CAT assay / DNA element / DNA binding protein / RNA binding protein / DNA polymorphism / Differentiation / Nuclear factor / 転写制御 / 転写後制御 / ヒト遺伝子 / プロモーター / サイレンサー
Research Abstract

In this research project, we mainly analyzed in detail regulatory elements and cellular protein factors involved in the regulation of the expression of human thymidylate synthase (TS) gene. It must have unique control features, since it is required for highly regulated expression in a cell.
First of all, we prepared many mutant DNA fragments from a specific DNA fragment derived from the region around the transcriptional initiation site of the human TS gene and analyzed promoter and cis-acting elements using the mutant DNA fragments. As the result, we identified promoter elements and several other regulatory elements in the region upstream from the major cap site. An unusual inverted repeat including a triple tandem repeat present in the region immediately upstream from an initiation codon ATG was also found to be necessary for the efficient expression of the human TS gene. In addition, the triple tandem repeat was revealed to be polymorphic with respect to the number of a repeat unit and the polymorphic DNAs were shown to differ in the expression activity of the human TS gene. Furthermore, a protein factor that bindsto an RNA fragment which corresponds to the region containing the inverted repeat was found to be present both in nuclear and cytoplasmic extracts. Finally, when human leukemia HL-60 cells differentiated into granulocytes by the retinoic acid treatment, a nuclear factor NF-TS3, that was found in our previous study and that binds to the region around the initiation codon ATG of the human TS gene was shown to increase soon after the cells started to differentiate.
We think that it is important to identify additional regulatory elements and protein factors involved in the regulation of the human TS gene expression and to reveal their roles, especially the quantitative change of the positive and negative regulatory factors in response to the alteration of the cellular environment.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Nobuyuki Horie: "Characterization of regulatory sequences and nuclear factors that function in cooperation with the promoter of the human thymidylate synthase gene" Biochim.Biophys.Acta. 1216. 409-416 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Keiichi Takeishi: "Cloning and strctural analysis of a human thymidylate synthase pseudogene splite by several Alu suquences" Nucleic Acids Symposium Series. 29. 141-142 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nobuyuki Horie: "Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5'-terminal regulatory region of the human gene for thymidylate synthase" Cell Struct.Funct.20. 191-197 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nobuyuki Horie: "Functional structure of the promoter region of the human thymidylate synthase gene and nuclear factors that regulate the expression of the gene" Nucleic Acids Symposium Series. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Horie, N., Chimoto, M., Nozawa, R.and Takeishi, K: "Characterization of regulatory sequences and nuclear factors that function in cooperation with the promoter of the human thymidylate synthase gene." Biochim.Biophys.Acta. 1216. 409-416 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeishi, K., Watanabe, Y., Isono, K.and Horie, N: "Cloning and structural analysis of a human thymidylate synthase pseudogene split by several Alu sequences." Nucleic Acids Symposium Series. No.29. 141-142 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Horie, N., Aiba, H., Oguro, K., Hojo, H.and Takeishi, K: "Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5' -terminal regulatory region of the human gene for thymidylate synthase." Cell Struct.Funct. 20. 191-197 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Horie, N.and Takeishi, K: "Functional structure of the promoter region of the human thymidylate synthase gene and nuclear factors that regulate the expression of the gene." Nucleic Acids Symposium Series. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nobuyuki Horie: "Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5'-terminal regulatory region of the human gene for thymidylate synthase" Cell Structure and Function. 20(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nobuyuki Horie: "Characterization of regulatory sequences and nuclearfactors that function in cooperation with the promoter of the human thymidylate synthase gene21GC01:Biochim.Biophys.Acta" 1216. 409-416 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akira Kuwayama: "Appearance of nuclear factors which interact with genes for myeloid calcium binding proteins (MRP-8 and MRP-14)in differentiated HL-60 cells" Blood. 81. 3116-3121 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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