Characterization of constitutive CTCF/cohesin loci: a possible role in establishing topological domains in mammalian genomes.
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.
Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC 27709, USA. li3@niehs.nih.gov.
Yuanyuan
Y
Li
Weichun
W
Huang
Liang
L
Niu
David M
DM
Umbach
Shay
S
Covo
Leping
L
Li
D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D002874:Chromosome Mapping; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D015894:Genome, Human; D006801:Humans; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology*
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D012097:Repressor Proteins