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2003 Fiscal Year Final Research Report Summary

Inhibition of enhancer-promoter interaction involved in the developmental-stage specific gene regulation

Research Project

Project/Area Number 13460149
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied molecular and cellular biology
Research InstitutionUniversity of Tsukuba

Principal Investigator

TANIMOTO Keiji  University of Tsukuba, Institute of applied biochemistry, associate professor, 応用生物化学系, 助教授 (90261776)

Co-Investigator(Kenkyū-buntansha) ISHIDA Junji  University of Tsukuba, Institute of applied biochemistry, assistant professor, 応用生物化学系, 講師 (30323257)
SUGIYAMA Fumihiro  University of Tsukuba, Institute of applied biochemistry, associate professor, 基礎医学系, 助教授 (90226481)
AKIYOSHI Fukamizu  University of Tsukuba, Institute of applied biochemistry, professor, 応用生物化学系, 教授 (60199172)
Project Period (FY) 2001 – 2003
Keywordsglobin / insulator / YAC / transgenic mouse
Research Abstract

The human (3-globin locus contains five developmentally regulated (3-type globin genes. All five genes depend on the locus control region (LCR), located at the 5' end of the locus, for abundant globin gene transcription. The LCR is composed of five DNase I hypersensitive sites (HSs), at least a subset of which appear to cooperate to form a holocomplex in activating genes within the locus. We previously tested the requirement for proper LCR polarity by inverting it in human β-globin YAC transgenic mice (TgM) and observed reduced expression of all the β-type globin genes, regardless of developmental stage. This phenotype clearly demonstrated an orientation-dependent activity of the LCR, although the mechanistic basis for the observed activity was obscure. In this research project, we obtained genetic evidence demonstrating that human HSS includes enhancer-blocking (insulator) activity that was dependent on the presence of an intact CTCF-binding motif within LCR HSS. Curiously, this CTCF-dependent activity appeared to be both gene and developmental-stage specific. These observations demonstrated that the phenotype observed in the LCR-inverted locus was, in part, attributable to placing the HSS insulator between the LCR HS "enhancers (HS1-4)" and the promoter of the β-globin gene, but further that the HS5 sequence also beared a primitive erythroid silencing activity that is CTCF-independent.

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] 田邊 修: "An embryonic/fetal beta-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer."EMBO J.. 21. 3434-3442 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 谷本啓司: "Human beta-globin locus control region HS5 contains CTCF- and developmental stage-dependent enhancer-blocking activity in erythroid cells."Molecular and Cellular Biology. 23. 8946-8952 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanabe O, Katsuoka F, Campbell AD, Sono W, Yamamoto M, Tanimoto K, Engel JD.: "An embryonic/fetal beta-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer"EMBO J.. 21. 3434-3442 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanimoto K, Sugiura A, Omori A, Fefsenfeld G, Engel JD, Fukamizu A.: "Human beta-globin locus control region HSS contains CTCF-and developmental stage-dependent enhancer-blocking activity in erythroid cells"Mol Cell Biol.. 23. 8946-8952 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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