Genome-wide binding studies reveal DNA binding specificity mechanisms and functional interplay amongst Forkhead transcription factors.
Genome-wide binding studies reveal DNA binding specificity mechanisms and functional interplay amongst Forkhead transcription factors.
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DOI：
10.1093/nar/gkv1120
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发表时间：
2016-02-29
影响因子：
14.9
通讯作者：
Sharrocks AD
中科院分区：
文献类型：
--
作者：
Chen X;Ji Z;Webber A;Sharrocks AD
属于相同转录因子家族的转录因子含有非常相似的DNA结合结构域，因此具有与相关DNA序列结合的潜力。然而，可以在体外检测到结合特异性的细微差异，并有可能在体内指导特异性反应。在这里，我们研究了三个叉头（FOX）转录因子，FOXK2，FOXO 3和FOXJ 3在体内的结合特性。观察到染色质结合的广泛重叠，尽管潜在的差异DNA结合特异性可以决定FOXK2和FOXJ3向染色质的募集。然而，在功能上，FOXO3依赖性基因调控通常不是通过独特的结合区域介导的，而是通过FOXK2和FOXO3占据的区域介导的，其中这两种因子都发挥调控作用。我们的数据点的模型，FOX转录因子控制基因表达，通过动态结合，并产生部分占用相同的网站，而不是相互排斥的结合所产生的稳定结合的个别FOX蛋白。
Transcription factors belonging to the same transcription factor families contain very similar DNA binding domains and hence have the potential to bind to related DNA sequences. However, subtle differences in binding specificities can be detected in vitro with the potential to direct specific responses in vivo. Here, we have examined the binding properties of three Forkhead (FOX) transcription factors, FOXK2, FOXO3 and FOXJ3 in vivo. Extensive overlap in chromatin binding is observed, although underlying differential DNA binding specificity can dictate the recruitment of FOXK2 and FOXJ3 to chromatin. However, functionally, FOXO3-dependent gene regulation is generally mediated not through uniquely bound regions but through regions occupied by both FOXK2 and FOXO3 where both factors play a regulatory role. Our data point to a model whereby FOX transcription factors control gene expression through dynamically binding and generating partial occupancy of the same site rather than mutually exclusive binding derived by stable binding of individual FOX proteins.