California Institute of Technology, Pasadena, CA 91125, USA.
Curr Top Microbiol Immunol. 2012;356:117-43. doi: 10.1007/82_2011_168.
T-cell development endows cells with a flexible range of effector differentiation options, superimposed on a stable core of lineage-specific gene expression that is maintained while access to alternative hematopoietic lineages is permanently renounced. This combination of features could be explained by environmentally responsive transcription factor mobilization overlaying an epigenetically stabilized base gene expression state. For example, "poising" of promoters could offer preferential access to T-cell genes, while repressive histone modifications and DNA methylation of non-T regulatory genes could be responsible for keeping non-T developmental options closed. Here, we critically review the evidence for the actual deployment of epigenetic marking to support the stable aspects of T-cell identity. Much of epigenetic marking is dynamically maintained or subject to rapid modification by local action of transcription factors. Repressive histone marks are used in gene-specific ways that do not fit a simple, developmental lineage-exclusion hierarchy. We argue that epigenetic analysis may achieve its greatest impact for illuminating regulatory biology when it is used to locate cis-regulatory elements by catching them in the act of mediating regulatory change.
T 细胞发育赋予细胞一系列灵活的效应分化选择，叠加在一个稳定的谱系特异性基因表达核心上，该核心在永久放弃对其他造血谱系的访问时得以维持。这种特征的组合可以通过环境响应转录因子的动员来解释，这种动员叠加在一个表观遗传稳定的基础基因表达状态上。例如，启动子的“启动”可以优先访问 T 细胞基因，而抑制性组蛋白修饰和非 T 调节基因的 DNA 甲基化可能负责关闭非 T 发育选择。在这里，我们批判性地回顾了表观遗传标记实际用于支持 T 细胞特性稳定方面的证据。大多数表观遗传标记是动态维持的，或者容易受到转录因子局部作用的快速修饰。抑制性组蛋白标记以特定于基因的方式使用，不适合简单的发育谱系排除层次结构。我们认为，当表观遗传分析用于通过捕捉它们在介导调节变化的过程中定位顺式调节元件时，它可能会在阐明调节生物学方面产生最大的影响。
