Essential Roles of SATB1 in Specifying T Lymphocyte Subsets
Essential Roles of SATB1 in Specifying T Lymphocyte Subsets
复制标题
DOI：
10.1016/j.celrep.2017.04.038
复制
发表时间：
2017-05-09
期刊：
影响因子：
8.8
通讯作者：
Taniuchi, Ichiro
中科院分区：
文献类型：
--
作者：
Kakugawa, Kiyokazu;Kojo, Satoshi;Taniuchi, Ichiro
I类和II类MHC的T细胞受体（TCR）信号传导分别通过诱导Runx 3和ThPOK转录因子诱导胸腺细胞获得细胞毒性和辅助命运。TCR信号转导被翻译成每个细胞命运的转录程序的机制仍然难以捉摸。在这里，我们表明，在选择后的胸腺细胞，基因组组织者，SATB 1，激活基因的谱系指定的因素，包括ThPOK，Runx3，CD4，CD8和Treg因子Foxp3，通过调节增强子在这些基因中的位点特异性的方式。事实上，SATB 1缺陷型胸腺细胞在MHC I类和II类介导的选择后部分重定向为不适当的T谱系，并且它们不能产生NKT和Treg亚群。尽管SATB 1在激活TCR信号转导的胸腺细胞中编码ThPOK的基因的增强子中起着重要作用，但它在维持CD4（+）T细胞中的ThPOK方面起着重要作用。总的来说，我们的研究结果表明，SATB 1形状的主要T细胞池，通过指导谱系特异性转录程序在胸腺。
T cell receptor (TCR) signaling by MHC class I and II induces thymocytes to acquire cytotoxic and helper fates via the induction of Runx3 and ThPOK transcription factors, respectively. The mechanisms by which TCR signaling is translated into transcriptional programs for each cell fate remain elusive. Here, we show that, in post-selection thymocytes, a genome organizer, SATB1, activates genes for lineage-specifying factors, including ThPOK, Runx3, CD4, CD8, and Treg factor Foxp3, via regulating enhancers in these genes in a locus-specific manner. Indeed, SATB1-deficient thymocytes are partially re-directed into inappropriate T lineages after both MHC class I-and II-mediated selection, and they fail to generate NKT and Treg subsets. Despite its essential role in activating enhancers for the gene encoding ThPOK in TCR-signaled thymocytes, SATB1 becomes dispensable for maintaining ThPOK in CD4(+) T cells. Collectively, our findings demonstrate that SATB1 shapes the primary T cell pool by directing lineage-specific transcriptional programs in the thymus.