The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus.
The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus.
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DOI：
10.1084/jem.20092024
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发表时间：
2009-11-23
期刊：
影响因子：
--
通讯作者：
Bosselut R
中科院分区：
文献类型：
--
作者：
Zamisch M;Tian L;Grenningloh R;Xiong Y;Wildt KF;Ehlers M;Ho IC;Bosselut R
转录因子Ets1有助于胸腺中CD8谱系细胞的分化，但其如何做到这一点尚不清楚。在这项研究中，我们证明，Ets1是必要的主要组织相容性1类（MHC I）限制性胸腺细胞的分化过程中的CD4表达的适当终止，但不为其他事件与他们的积极选择，包括启动细胞毒性基因表达，皮质髓质迁移，或胸腺出口。我们进一步表明，Ets1促进Runx3的表达，Runx3是一种对CD8 T细胞分化和Cd4基因表达停止很重要的转录因子。在Ets1缺陷型MHC I限制性胸腺细胞中，Runx3的强制表达在很大程度上挽救了受损的Cd4沉默，表明Ets1对Runx3功能不是必需的。最后，我们的文件Ets1结合至少两个进化保守的区域内的Runx3基因在体内，支持Ets1直接有助于Runx3转录的可能性。这些发现确定Ets1作为CD8谱系分化过程中的关键参与者，并表明它至少部分通过促进Runx3表达起作用。
The transcription factor Ets1 contributes to the differentiation of CD8 lineage cells in the thymus, but how it does so is not understood. In this study, we demonstrate that Ets1 is required for the proper termination of CD4 expression during the differentiation of major histocompatability class 1 (MHC I)–restricted thymocytes, but not for other events associated with their positive selection, including the initiation of cytotoxic gene expression, corticomedullary migration, or thymus exit. We further show that Ets1 promotes expression of Runx3, a transcription factor important for CD8 T cell differentiation and the cessation of Cd4 gene expression. Enforced Runx3 expression in Ets1-deficient MHC I–restricted thymocytes largely rescued their impaired Cd4 silencing, indicating that Ets1 is not required for Runx3 function. Finally, we document that Ets1 binds at least two evolutionarily conserved regions within the Runx3 gene in vivo, supporting the possibility that Ets1 directly contributes to Runx3 transcription. These findings identify Ets1 as a key player during CD8 lineage differentiation and indicate that it acts, at least in part, by promoting Runx3 expression.
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