Functional diversity of CTCFs is encoded in their binding motifs

BMC Genomics
Rongxin FangZhihua Zhang

Abstract

The 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. Here, 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. These 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...Continue Reading

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Citations

Feb 16, 2016·Genomics, Proteomics & Bioinformatics·Zhihua Zhang
Dec 15, 2015·Seminars in Cell & Developmental Biology·Chenhuan Xu, Victor G Corces
Jun 18, 2016·Blood·Benedetta IzziMarc F Hoylaerts
Oct 31, 2019·Nucleic Acids Research·Christopher T ClarksonVladimir B Teif
Jul 25, 2019·JCI Insight·Iris K Madera-SalcedoJosé C Crispín

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Datasets Mentioned

BETA
GM12878
cells

Methods Mentioned

BETA
immunoprecipitation
ChIP-seq
RNA-seq

Software Mentioned

FIMO
ENSEMBLE
Motif Logo
MACS

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