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Analysis of molecular dynamics of constitutive KLF induction through chromatin conformation change by statin

Research Project

Project/Area Number 23659050
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

WADA Youichiro  東京大学, 先端科学技術研究センター, 特任准教授 (10322033)

Project Period (FY) 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywordsスタチン / 転写調節 / KLFファミリー / 内皮細胞 / 動脈硬化
Research Abstract

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, are known to exert athero-protective effects through the induction of specific transcriptional factors in multiple organs. Here, we focus on the beneficial effect in vascular wall, and analyzed comprehensive gene expression profile induced by pitavastatin. Through microarray analysis, we identified KLF4 and KLF2 as significantly induced genes. Using the chromatin immunoprecipitation with deep sequencing(ChIP-seq) analysis, we identified a novel functionally important MEF2C binding site within KLF4 gene. Chromatin conformation analysis revealed this MEF2C-bound enhancer had spacial proximity to transcription start site and the frequency was increased by pitavastatin treatment. Thus, in statin treated endothelium, MEF2C was activated through MEK5/ERK5 pathway, and spacial proximity of MEF2C occupied enhancer was increased in KLF4 induction, suggesting dynamic chromatin conformation change was involved in statin mediated gene induction.

Report

(2 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (12 results)

All 2012 2011

All Journal Article (6 results) (of which Peer Reviewed: 4 results) Presentation (6 results)

  • [Journal Article] Distribution of histone3 lysine4 trimethylation at T3-responsive loci in the heart during reversible changes in gene expression2012

    • Author(s)
      Pandya K, Kohro T, Wada Y, et al
    • Journal Title

      Gene Expression, in press

    • Related Report
      2011 Final Research Report
  • [Journal Article] Dynamic change of the chromatin conformation in response to hypoxia enhances the expression of GLUT3(SLC2A3) by cooperative interaction of HIF1 and KDM3A2012

    • Author(s)
      Mimura I, Wada Y, et al
    • Journal Title

      Molecular and Cellular Biology, in press

    • Related Report
      2011 Final Research Report
  • [Journal Article] Distribution of histone3 lysine4 trimethylation at T3-responsive loci in the heart during reversible changes in gene expression2012

    • Author(s)
      Pandya K, Kohro T, Wada Y, et al
    • Journal Title

      Gene Expression

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetically coordinated GATAT2 binding is necessary for endothelium-specific endomucin expression2011

    • Author(s)
      Kanki Y, Kohro T, Jiang S, Tsutsumi S, Mimura I, Suehiro J, Wada Y, Ohta Y, Ihara S, Iwanari H, Naito M, Hamakubo T, Aburatani H, Kodama T, Minami T
    • Journal Title

      EMBO J

      Volume: 30 Issue: 13 Pages: 2582-95

    • DOI

      10.1038/emboj.2011.173

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide approaches reveal functional interleukin-4-inducible STAT6 binding to the vascular cell adhesion molecule 1 promoter.2011

    • Author(s)
      Tozawa H, Kanki Y, Wada Y, et al.
    • Journal Title

      Molecular and Cellular Biology

      Volume: vol.31 Issue: 11 Pages: 2196-209

    • DOI

      10.1128/mcb.01430-10

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial DNA polymerase editing mutation, PolgD257A, reduces the diabetic phenotype of Akita male mice by suppressing appetite.2011

    • Author(s)
      Fox, R., Kim, H. S., Reddick, R. L., Kujoth, G. C., Prolla, T. A., Tsutsumi, S., Wada, Y., Smithies, O., and *Maeda, N.
    • Journal Title

      Proceedings of the National Academy ofSciences of the United States of America

      Volume: 108 Issue: 21 Pages: 8779-8784

    • DOI

      10.1073/pnas.1106344108

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Presentation] A wave of nascent transcription on activated big genes in human endothelial cells2012

    • Author(s)
      和田洋一郎
    • Organizer
      Keystone Symposia 2012 Chromatin Dynamics
    • Related Report
      2011 Final Research Report
  • [Presentation] A wave of nascent transcription on activated big genes in human endothelial cells2012

    • Author(s)
      和田洋一郎
    • Organizer
      Keystone Symposia 2012 Chromation Dynamics
    • Place of Presentation
      Keystone Colorado, U.S.A
    • Related Report
      2011 Annual Research Report
  • [Presentation] 超高速シーケンサーが明らかにした転写に伴うダイナミックな染色体構造変化と新たな転写装置の概念2011

    • Author(s)
      和田洋一郎
    • Organizer
      第2回ARTセミナー
    • Place of Presentation
      岡山大学
    • Year and Date
      2011-05-25
    • Related Report
      2011 Final Research Report
  • [Presentation] 超高速シーケンサーが明らかにした転写に伴うダイナミックな染色体構造変化と新たな転写装置の概念2011

    • Author(s)
      和田洋一郎
    • Organizer
      第2回ARTセミナー
    • Place of Presentation
      岡山大学(招待講演)
    • Year and Date
      2011-05-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] Renewal of histone modification during a wave of transcription caused by inflammatory stimulation in endothelial cells2011

    • Author(s)
      和田洋一郎
    • Organizer
      第5回日本エピジェネティクス研究会
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Identification of novel MEF2C binding site indispensable for KLF4 induction in endothelial cells by statin treatment2011

    • Author(s)
      前島崇司、和田洋一郎
    • Organizer
      第19回日本血管生物医学会学術集会
    • Place of Presentation
      東京ステーションコンファレンス、東京
    • Related Report
      2011 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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