NFAT Is Well Placed to Direct Both Enhancer Looping and Domain-Wide Models of Enhancer Function
NFAT Is Well Placed to Direct Both Enhancer Looping and Domain-Wide Models of Enhancer Function
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DOI：
10.1126/stke.113pe15
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发表时间：
2008-04-01
影响因子：
7.3
通讯作者：
Cockerill, Peter N.
中科院分区：
文献类型：
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作者：
Cockerill, Peter N.
活化T细胞核因子（NFAT）在染色质结构水平上激活基因表达中起着核心作用。现在的一项研究表明，NFAT也可能有助于组织染色质结构域并实现增强子-启动子通信。在活化的T细胞中，可诱导的染色体内成环发生在肿瘤坏死因子-α（TNF-α）基因启动子和位于-9 kb和+3 kb的两个NFAT依赖性增强子之间。这种拓扑结构将TNF-α基因和相邻的α-光毒素基因置于单独的环中，从而允许TNF-α基因在多基因位点内的独立调节。这些发现建立在其他研究的基础上，这些研究表明NFAT与破坏增强子内的核小体并在连接增强子和启动子的广泛染色质结构域中动员核小体的活性密切相关。总之，这些研究突出了NFAT作为一种因子，其创造了允许在启动子和增强子处控制转录的因子的募集和聚集的染色质环境。
Nuclear factor of activated T cells (NFAT) plays a central role in activating gene expression at the level of chromatin structure. A study now reveals that NFAT may also help to organize chromatin domains and enable enhancer-promoter communication. In activated T cells, inducible intrachromosomal looping occurs between the tumor necrosis factor-alpha (TNF-alpha) gene promoter and two NFAT-dependent enhancers located at -9 kb and +3 kb. This topology places the TNF-alpha gene and the adjacent lymphotoxin genes in separate loops, thereby allowing independent regulation of the TNF-alpha gene within a multigene locus. These findings build on other studies that indicate that NFAT is intimately associated with activities that disrupt nucleosomes within enhancers and mobilize nucleosomes across extensive chromatin domains linking enhancers and promoters. Taken together, these studies highlight NFAT as a factor that creates a chromatin environment that is permissive for both the recruitment and the clustering of factors that control transcription at promoters and enhancers.