SATB1 is required for CD8 coreceptor reversal.

SATB1 is required for CD8 coreceptor reversal.
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DOI:
10.1016/j.molimm.2008.07.007
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发表时间:
2008-11
影响因子:
3.6
通讯作者:
Tucker PW
Tucker PW
中科院分区:
医学3区
文献类型:
--
作者:
Nie H;Yao X;Maika SD;Tucker PW

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Intrathymic signals induce the differentiation of immature CD4+CD8+ double positive (DP) thymocytes into mature CD4+ or CD8+ single positive (SP) T cells. The transcriptional mechanism by which CD8 lineage is determined is not fully understood. The best evidence, which favors the kinetic signaling/co-receptor reversal model, indicates that signaled DP thymocytes terminate CD8 transcription prior to their subsequent re-initiation of CD8 transcription and ultimate differentiation into CD8SP T cells. We and others have shown that CD8 lineage commitment is severely perturbed in mice in which expression of the transcription factor SATB1 is either conventionally knocked out or T cell-specifically knocked down. Here, we demonstrate that, as with normal thymocytes, cultured SATB1-deficient DP thymocytes inactivate CD8 coreceptor transcription following receipt of signals (PMA plus ionomycin) that mimic TCR-mediated positive selection. However, this terminated CD8 transcription is not re-initiated by signals (IL-7) conducive to CD8 differentiation in SATB1-deficient DP. We show that SATB1 specifically binds to a cis-regulatory element within the CD8 enhancer (E8III) known to be required for coreceptor reversal. A requirement in CD8 coreceptor reversal identifies SATB1 as an essential trans-regulator of CD8 lineage fate, whose action may be mediated via recruitment to the E8III DP enhancer.
在Jurkat T细胞中与特殊富含富含富含良好的序列结合蛋白1(SATB1)结合的基因组序列与染色质环的底部的核基质紧密相关。
DOI: 10.1083/jcb.141.2.335
发表时间: 1998-04-20
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