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Analysis of Bcl11b function during thymocyte Differentiation

Research Project

Project/Area Number 22790478
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

TANAKA Hirokazu  独立行政法人理化学研究所, 免疫転写制御研究グループ, 基礎科学特別研究員 (50569556)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsリンパ球分化 / T細胞 / 転写因子 / リンパ球 / 遺伝子発現制御 / 胸腺細胞 / BCl11b転写因子 / Runx転写因子
Research Abstract

It has been shown that any post-selection DP thymocytes differentiate into CD4-lineage upon expression of ThPOK, whereas they become CD8-linage cells in the absence of ThPOK. Therefore it is crucial to understand how helper-lineage specific expression of ThPOK gene is regulated. We have identified a ThPOK silencer in the ThPOK gene that is essential to repress ThPOK gene during differentiation of MHC class I selected cells toward the cytotoxic-lineage.
In order to reveal regulation of ThPOK silencer activity, we performed pull down affinity purification with the functional shorter silencer sequences. After molecular and biological screening of several candidates obtained by the above approach, Bcl11b transcription factor appeared to play an essential role in activating ThPOK silencer. Genetic analysis of Bcl11b conditional knock-out mice showed that de-repression of ThPOK in both pre-selection thymocyte and in MHC class I selected cells, resulting in cell fate conversion of MHC class I selected cells to CD4^+helper lineage cells. These results suggested that Bcl11b is central to regulate helper/cytotoxic lineage decision by lymphocytes via regulation of ThPOK silencer activity.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (6 results)

All 2012 2011 2010

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (4 results)

  • [Journal Article] Roles of VWRPY motif-mediated gene repression by Runx proteins during T-cell development2012

    • Author(s)
      Seo W, Tanaka H, Miyamoto C, Levanon D, Groner Y, Taniuchi I
    • Journal Title

      Immunol Cell Biol

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional control of T-cell development2011

    • Author(s)
      Naito T, Tanaka H, Naoe Y, Taniuchi I
    • Journal Title

      Int Immunol

      Volume: 23(11) Pages: 661-8

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] The role of Bcl11b in lineage commitment of CD4+CD8+DP thymocytes via regulation of ThPOK silencer activity2011

    • Author(s)
      田中宏和
    • Organizer
      日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Year and Date
      2011-11-27
    • Related Report
      2011 Final Research Report
  • [Presentation] The role of Bcl11b in lineage commitment of CD4+CD8+DP thymocytes via regulation of ThPOK silencer activity2011

    • Author(s)
      田中宏和
    • Organizer
      日本免疫学会
    • Place of Presentation
      幕張
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification and functional characterization of ThPOK silencer binding factors2011

    • Author(s)
      田中宏和
    • Organizer
      Chromatin Structure, Organization and Function (EMBO workshop)
    • Place of Presentation
      プラハ(チェコ共和国)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Cis- and trans- actimg factors regulating the ThPOK silencer activity2010

    • Author(s)
      田中宏和
    • Organizer
      第14回国際免疫学会議
    • Place of Presentation
      神戸
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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