Dual functions of Runx proteins for reactivating CD8 and silencing CD4 at the commitment process into CD8 thymocytes
Dual functions of Runx proteins for reactivating CD8 and silencing CD4 at the commitment process into CD8 thymocytes
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DOI：
10.1016/j.immuni.2005.01.012
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发表时间：
2005-03-01
期刊：
影响因子：
32.4
通讯作者：
Habu, S
中科院分区：
文献类型：
--
作者：
Sato, T;Ohno, S;Habu, S
为了了解在胸腺中从CD 4（+）8（+）（CD 4和CD 8双阳性，DP）细胞到CD 4（-）8（+）（CD 8单阳性，CD 8 SP）细胞的转变过程中如何调节CD 8表达，研究了Runx蛋白在染色质构型改变中的参与。使用染色质免疫沉淀试验，我们首先证明，Runx蛋白结合的阶段特异性CD 8增强子，以及CD 4沉默，在CD 8 SP胸腺细胞。在Runx家族成员中，Runx 3表达在接受阳性选择信号的DID胸腺细胞中启动，并随着向CD 8 SP阶段的分化而增加。此外，CD 8基因的再激活，以及CD 4沉默，被抑制在Runx显性阴性转基因小鼠的阳性选择的胸腺细胞。这些结果表明Flunx蛋白，尤其是Runx 3，参与CD 8 T细胞的谱系特化，并为了解成熟胸腺细胞中辅助受体相互排斥表达的机制提供了重要信息。
To understand how CD8 expression is regulated during the transition process from CD4(+)8(+) (CD4 and CD8 double positive, DP) to CD4(-)8(+) (CD8 single positive, CD8SP) cells in the thymus, the involvement of Runx proteins in the alteration of chromatin configuration was investigated. Using the chromatin immunoprecipitation assay, we first demonstrated that Runx proteins bind to the stage-specific CD8 enhancer, as well as the CD4 silencer, in CD8SP thymocytes. Among Runx family members, Runx3 expression was initiated in DID thymocytes receiving a positive selection signal and increased in concert with differentiation to the CD8SP stage. Furthermore, reactivation of the CD8 gene, as well as CD4 silencing, was suppressed in positively selected thymocytes of Runx dominant-negative transgenic mice. These results suggest that Flunx proteins, especially Runx3, are involved in lineage specification of CD8 T cells and provide important information for understanding the mechanism for the mutually exclusive expression of coreceptors in mature thymocytes.