Transcriptional and epigenetic control of T helper cell specification: molecular mechanisms underlying commitment and plasticity.
Transcriptional and epigenetic control of T helper cell specification: molecular mechanisms underlying commitment and plasticity.
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DOI：
10.1146/annurev-immunol-020711-075058
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发表时间：
2012
影响因子：
29.7
通讯作者：
O'Shea JJ
中科院分区：
文献类型：
--
作者：
Kanno Y;Vahedi G;Hirahara K;Singleton K;O'Shea JJ
辅助性T细胞分化发生在细胞外细胞因子环境的背景下，由多种微生物和其他致病刺激以及T细胞受体刺激引起。这些信号的最终结果是辅助性T谱系的确定，这是通过多种转录因子的组合作用产生的，这些转录因子建立了独特的转录组。通过这种方式，可诱导的，但构成活跃的主调控因子与信号换能器和转录激活器（STATs）等因子一起工作，感知细胞外环境。独特转录组的获得也依赖于影响关键顺式元件的染色质修饰以及全球基因组组织的变化。因此，信号转导和表观遗传学在这些分化过程中是联系在一起的。在这篇综述中，总结了最近在理解T辅助谱系规范和转录因子作用方面的进展，重点介绍了动态T细胞表观基因组的综合观点。
Helper T cell differentiation occurs in the context of the extracelluar cytokine milieu evoked by diverse microbes and other pathogenic stimuli along with T cell receptor stimulation. The culmination of these signals results in specification of T helper lineages, which occurs through the combinatorial action of multiple transcription factors that establish distinctive transcriptomes. In this manner, inducible, but constitutively active master regulators work in conjunction with factors like the signal transducer and activator of transcriptions (STATs) that sense the extracellular environment. The acquisition of distinctive transcriptome is also dependent upon chromatin modifications that impact key cis elements as well as the changes in global genomic organization. Thus, signal transduction and epigenetics are linked in these processes of differentiation. In this review, recent advances in understanding T helper lineage specification and deciphering the action of transcription factors are summarized with emphasis on comprehensive views of the dynamic T cell epigenome.
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