Functional diversity of CTCFs is encoded in their binding motifs.
Functional diversity of CTCFs is encoded in their binding motifs.
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CTCF 的功能多样性编码在其结合基序中
DOI：
10.1186/s12864-015-1824-6
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发表时间：
2015-08-28
期刊：
影响因子：
4.4
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Fang R;Wang C;Skogerbo G;Zhang Z
背景CCCCTC结合因子（CTCF）具有多种调节功能。然而，其功能多样性所需的 CTCF 结合基序的明确特征仍然难以捉摸。结果在这里，我们描述了一种新的基序发现工作流程，通过该工作流程，我们鉴定了具有高度不同功能的三个 CTCF 结合基序变体。在转录组、表观基因组和染色质相互作用数据的支持下，我们表明 CTCF 结合基序的功能多样性与其 GC 含量、CpG 二核苷酸覆盖度和第 12 区相对 DNA 甲基化水平密切相关。主题的位置。进一步分析表明，粘连蛋白（姐妹染色单体粘连的关键因素）的共定位与 CpG 覆盖度和第 12 位 DNA 相对甲基化水平呈负相关。最后，我们提出了一个假设模型的证据，其中启动子和远端调控区之间的染色质相互作用可能是由 CTCF 与高 CpG 序列结合介导的。结论这些结果证明存在与 CTCF 不同功能相对应的明确 CTCF 结合基序，并且基序的功能多样性与基序第 12 位的遗传和表观遗传特征密切相关。
BackgroundThe CCCTC-binding factor (CTCF) has diverse regulatory functions. However, the definitive characteristics of the CTCF binding motif required for its functional diversity still remains elusive.ResultsHere, we describe a new motif discovery workflow by which we have identified three CTCF binding motif variations with highly divergent functionalities.Supported by transcriptomic, epigenomic and chromatin-interactomic data, we show that the functional diversity of the CTCF binding motifs is strongly associated with their GC content, CpG dinucleotide coverage and relative DNA methylation level at the 12th position of the motifs. Further analysis suggested that the co-localization of cohesin, the key factor in cohesion of sister chromatids, is negatively correlated with the CpG coverage and the relative DNA methylation level at the 12th position. Finally, we present evidences for a hypothetical model in which chromatin interactions between promoters and distal regulatory regions are likely mediated by CTCFs binding to sequences with high CpG.ConclusionThese results demonstrate the existence of definitive CTCF binding motifs corresponding to CTCF’s diverse functions, and that the functional diversity of the motifs is strongly associated with genetic and epigenetic features at the 12th position of the motifs.