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

Yuanyuan Li, Weichun Huang, Liang Niu, David M. Umbach, Shay Covo, Leping Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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.

Original languageAmerican English
Article number553
JournalBMC Genomics
Volume14
Issue number1
DOIs
StatePublished - 14 Aug 2013

Bibliographical note

Funding Information:
This research was supported by Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ES101765).

Keywords

  • CTCF
  • Chromatin interaction
  • Cohesin
  • Constitutive binding site
  • Topological domain

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