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BMC Genomics. 2013 Aug 14;14:553. doi: 10.1186/1471-2164-14-553.

Characterization of constitutive CTCF/cohesin loci: a possible role in establishing topological domains in mammalian genomes.

Author information

1
Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC 27709, USA. li3@niehs.nih.gov.

Abstract

BACKGROUND:

Recent studies suggested that human/mammalian genomes are divided into large, discrete domains that are units of chromosome organization. CTCF, a CCCTC binding factor, has a diverse role in genome regulation including transcriptional regulation, chromosome-boundary insulation, DNA replication, and chromatin packaging. It remains unclear whether a subset of CTCF binding sites plays a functional role in establishing/maintaining chromatin topological domains.

RESULTS:

We systematically analysed the genomic, transcriptomic and epigenetic profiles of the CTCF binding sites in 56 human cell lines from ENCODE. We identified ~24,000 CTCF sites (referred to as constitutive sites) that were bound in more than 90% of the cell lines. Our analysis revealed: 1) constitutive CTCF loci were located in constitutive open chromatin and often co-localized with constitutive cohesin loci; 2) most constitutive CTCF loci were distant from transcription start sites and lacked CpG islands but were enriched with the full-spectrum CTCF motifs: a recently reported 33/34-mer and two other potentially novel (22/26-mer); 3) more importantly, most constitutive CTCF loci were present in CTCF-mediated chromatin interactions detected by ChIA-PET and these pair-wise interactions occurred predominantly within, but not between, topological domains identified by Hi-C.

CONCLUSIONS:

Our results suggest that the constitutive CTCF sites may play a role in organizing/maintaining the recently identified topological domains that are common across most human cells.

PMID:
23945083
PMCID:
PMC3765723
DOI:
10.1186/1471-2164-14-553
[Indexed for MEDLINE]
Free PMC Article

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