Functional diversity of CTCFs is encoded in their binding motifs

BMC Genomics

Research Article

Geir Skogerbo¹  Rongxin Fang²  Chengqi Wang²  Zhihua Zhang² 

[1] Bioinformatics Laboratory and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101, Beijing, China;

关键词: CTCF;    Binding motif;    DNA methylation;    Chromatin interaction;   

DOI  :  10.1186/s12864-015-1824-6

 received in 2014-09-12, accepted in 2015-08-07,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Fang et al. 2015