Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genome Biol. 2009;10(11):R131. doi: 10.1186/gb-2009-10-11-r131. Epub 2009 Nov 18.

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

Author information

  • 1Penn Center for Bioinformatics, Department of Genetics, 415 Curie Boulevard, University of Pennsylvania, Philadelphia, PA 19104, USA. kobby@pcbi.upenn.edu

Abstract

BACKGROUND:

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.

RESULTS:

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.

CONCLUSIONS:

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

PMID:
19922652
[PubMed - indexed for MEDLINE]
PMCID:
PMC3091324
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Write to the Help Desk