Analysis of Bcl11b function during thymocyte Differentiation

Bcl11b在胸腺细胞分化过程中的功能分析

• 批准号: 22790478
• 负责人: TANAKA Hirokazu
• 金额: $ 2.5万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790478/
• 关键词: 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

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.

研究表明，任何选择后的 DP 胸腺细胞在表达 ThPOK 时都会分化为 CD4 谱系细胞，而在缺乏 ThPOK 的情况下它们会分化为 CD8 谱系细胞。因此，了解 ThPOK 基因的辅助谱系特异性表达是如何调控的至关重要。我们在 ThPOK 基因中发现了一个 ThPOK 沉默子，它对于在 MHC I 类选择的细胞向细胞毒性谱系分化过程中抑制 ThPOK 基因至关重要。更短的消音器序列。对通过上述方法获得的几个候选物进行分子和生物学筛选后，Bcl11b转录因子似乎在激活ThPOK沉默子中发挥重要作用。 Bcl11b条件敲除小鼠的遗传分析表明，预选胸腺细胞和MHC I类选择细胞中ThPOK的去抑制，导致MHC I类选择细胞的细胞命运转变为CD4^+辅助谱系细胞。这些结果表明，Bcl11b 通过调节 ThPOK 沉默子活性来调节淋巴细胞的辅助/细胞毒性谱系决策。

项目成果

The role of Bcl11b in lineage commitment of CD4+CD8+DP thymocytes via regulation of ThPOK silencer activity

Bcl11b 通过调节 ThPOK 沉默子活性在 CD4 CD8 DP 胸腺细胞谱系定型中的作用

• 发表时间: 2011
• 作者: 田中宏和

Cis- and trans- actimg factors regulating the ThPOK silencer activity

调节 ThPOK 沉默子活性的顺式和反式激活因子

• 发表时间: 2010
• 作者: 田中宏和

Roles of VWRPY motif-mediated gene repression by Runx proteins during T-cell development

Runx 蛋白在 T 细胞发育过程中 VWRPY 基序介导的基因抑制的作用

• 发表时间: 2012
• 影响因子: 4
• 作者: Seo W; Tanaka H; Miyamoto C; Levanon D; Groner Y; Taniuchi I
• 通讯作者: Taniuchi I

Transcriptional control of T-cell development

T 细胞发育的转录控制

• 发表时间: 2011
• 影响因子: 4.4
• 作者: Naito T; Tanaka H; Naoe Y; Taniuchi I
• 通讯作者: Taniuchi I

The role of Bcl11b in lineage commitment of CD4+CD8+DP thymocytes via regulation of ThPOK silencer activity

Bcl11b 通过调节 ThPOK 沉默子活性在 CD4 CD8 DP 胸腺细胞谱系定型中的作用

• 发表时间: 2011
• 作者: 田中宏和