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.