Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development
Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development
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DOI：
10.1126/science.1151844
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发表时间：
2008-02-08
期刊：
影响因子：
56.9
通讯作者：
Taniuchi, Ichiro
中科院分区：
文献类型：
--
作者：
Setoguchi, Ruka;Tachibana, Masashi;Taniuchi, Ichiro
小鼠CD 4（+）CD 8（+）双阳性（DP）胸腺细胞在转录因子Th-POK表达后分化为CD 4（+）辅助细胞系，但在其缺失时定向为CD 8（+）细胞毒性细胞系.我们报道了Runx转录因子复合物缺失后，I类限制性胸腺细胞向CD 4（+）CD 8（-）辅助样T细胞的重定向分化。Th-POK基因座内的Runx结合序列作为转录沉默子起作用，其对于Th-POK抑制和CD 8（+）T细胞的发育是必需的.因此，Th-POK表达和T辅助细胞发育的遗传编程被Runx依赖性沉默子活性主动抑制，从而允许细胞毒性T细胞分化. CD 4和CD 8谱系选择中转录因子网络的鉴定提供了对不同T细胞亚群如何发展以调节适应性免疫系统的深入了解。
Mouse CD4(+) CD8(+) double- positive ( DP) thymocytes differentiate into CD4(+) helper- lineage cells upon expression of the transcription factor Th- POK but commit to the CD8(+) cytotoxic lineage in its absence. We report the redirected differentiation of class I - restricted thymocytes into CD4(+) CD8(-) helper- like T cells upon loss of Runx transcription factor complexes. A Runx- binding sequence within the Th- POK locus acts as a transcriptional silencer that is essential for Th- POK repression and for development of CD8(+) T cells. Thus, Th- POK expression and genetic programming for T helper cell development are actively inhibited by Runx- dependent silencer activity, allowing for cytotoxic T cell differentiation. Identification of the transcription factors network in CD4 and CD8 lineage choice provides insight into how distinct T cell subsets are developed for regulating the adaptive immune system.