Lee Gap Ryol, Kim Sean T, Spilianakis Charalampos G, Fields Patrick E, Flavell Richard A
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Immunity. 2006 Apr;24(4):369-79. doi: 10.1016/j.immuni.2006.03.007.
Cytokine loci undergo changes in chromatin structure when naive CD4(+) T cells differentiate into Th1 or Th2 cells and have also been examined for regulatory sequences underlying such changes and their functional correlates. Studies have shown that distal regulatory elements control the Ifng and Th2 cytokine loci and are primary targets for tissue-specific transcription factors, serving as centers for epigenetic changes that mark heritable traits in effector cells. Reports of intra- and, remarkably, interchromosomal interactions between these regulatory elements shed light on the mechanisms by which they regulate gene expression, revealing an extraordinary new picture that conceptually extends our views on how genes are regulated from two to three dimensions. Here, we summarize these recent findings on the role of regulatory elements and their mechanisms of action, which are of broad significance for gene regulation, not only of the immune system but also of many, if not all, coregulated genes.
当初始CD4(+) T细胞分化为Th1或Th2细胞时，细胞因子基因座的染色质结构会发生变化，并且人们也对这些变化背后的调控序列及其功能相关性进行了研究。研究表明，远端调控元件控制着Ifng和Th2细胞因子基因座，是组织特异性转录因子的主要作用靶点，作为表观遗传变化的中心，这些变化标记了效应细胞中的可遗传特征。关于这些调控元件之间的染色体内以及，值得注意的是，染色体间相互作用的报道揭示了它们调控基因表达的机制，展现出一幅非凡的新图景，从概念上把我们对基因调控的认识从二维扩展到了三维。在此，我们总结了这些关于调控元件的作用及其作用机制的最新发现，这些发现不仅对免疫系统的基因调控，而且对许多（如果不是全部的话）共同调控基因的基因调控都具有广泛的意义。
