Analysis of Bcl11b function during thymocyte Differentiation
| Project/Area Number |
22790478
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | The Institute of Physical and Chemical Research |
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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)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| 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)
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| 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 |
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| 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.
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Report
(3 results)
Research Products
(6 results)
