Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development
Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development
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DOI：
10.1016/s0092-8674(02)01111-x
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发表时间：
2002-11-27
期刊：
影响因子：
64.5
通讯作者：
Littman, DR
中科院分区：
文献类型：
--
作者：
Taniuchi, I;Osato, M;Littman, DR
T淋巴细胞在胸腺内分化为不连续的阶段。缺乏CD 4和CD 8辅助受体的未成熟胸腺细胞分化为双阳性细胞（CD 4（+）CD 8（+）），其被选择成为CD 4（+）CD 8（-）辅助细胞或CD 4（-）CD 8（+）细胞毒性细胞。阶段特异性转录沉默子调节未成熟和CD 4（-）CD 8（+）胸腺细胞中CD 4的表达我们在这里表明，Runt结构域转录因子的结合位点是必不可少的CD 4沉默功能在这两个阶段，并需要不同的Runx家族成员，以履行独特的功能，在每个阶段。Runxi是CD 4（-）CD 8（-）胸腺细胞中主动抑制所必需的，而Runx 3是在细胞毒性谱系胸腺细胞中建立表观遗传沉默所必需的。Runx 3缺陷的细胞毒性T细胞，而不是辅助细胞，有缺陷的抗原反应，表明Runx蛋白在谱系规范和稳态的CD 8谱系T淋巴细胞的关键功能。
T lymphocytes differentiate in discrete stages within the thymus. Immature thymocytes lacking CD4 and CD8 coreceptors differentiate into double-positive cells (CD4(+)CD8(+)), which are selected to become either CD4(+)CD8(-)helper cells or CD4(-)CD8(+) cytotoxic cells. A stage-specific transcriptional silencer regulates expression of CD4 in both immature and CD4(-)CD8(+) thymocytes. We show here that binding sites for Runt domain transcription factors are essential for CD4 silencer function at both stages, and that different Runx family members are required to fulfill unique functions at each stage. Runxi is required for active repression in CD4(-)CD8(-) thymocytes whereas Runx3 is required for establishing epigenetic silencing in cytotoxic lineage thymocytes. Runx3-deficient cytotoxic T cells, but not helper cells, have defective responses to antigen, suggesting that Runx proteins have critical functions in lineage specification and homeostasis of CD8lineage T lymphocytes.