Email updates

Keep up to date with the latest news and content from Genome Biology and BioMed Central.

Open Access Research

CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features

Kobby Essien1, Sebastien Vigneau2, Sofia Apreleva1, Larry N Singh1, Marisa S Bartolomei2 and Sridhar Hannenhalli1*

Author Affiliations

1 Penn Center for Bioinformatics, Department of Genetics, 415 Curie Boulevard, University of Pennsylvania, Philadelphia, PA 19104, USA

2 Department of Cell and Developmental Biology, 421 Curie Boulevard, University of Pennsylvania, Philadelphia, PA 19104, USA

For all author emails, please log on.

Genome Biology 2009, 10:R131  doi:10.1186/gb-2009-10-11-r131

Published: 18 November 2009



CTCF (CCCTC-binding factor) is an evolutionarily conserved zinc finger protein involved in diverse functions ranging from negative regulation of MYC, to chromatin insulation of the beta-globin gene cluster, to imprinting of the Igf2 locus. The 11 zinc fingers of CTCF are known to differentially contribute to the CTCF-DNA interaction at different binding sites. It is possible that the differences in CTCF-DNA conformation at different binding sites underlie CTCF's functional diversity. If so, the CTCF binding sites may belong to distinct classes, each compatible with a specific functional role.


We have classified approximately 26,000 CTCF binding sites in CD4+ T cells into three classes based on their similarity to the well-characterized CTCF DNA-binding motif. We have comprehensively characterized these three classes of CTCF sites with respect to several evolutionary, genomic, epigenomic, transcriptomic and functional features. We find that the low-occupancy sites tend to be cell type specific. Furthermore, while the high-occupancy sites associate with repressive histone marks and greater gene co-expression within a CTCF-flanked block, the low-occupancy sites associate with active histone marks and higher gene expression. We found that the low-occupancy sites have greater conservation in their flanking regions compared to high-occupancy sites. Interestingly, based on a novel class-conservation metric, we observed that human low-occupancy sites tend to be conserved as low-occupancy sites in mouse (and vice versa) more frequently than expected.


Our work reveals several key differences among CTCF occupancy-based classes and suggests a critical, yet distinct functional role played by low-occupancy sites.