Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome.
Insulator elements affect gene expression by preventing the spread of heterochromatin and restricting transcriptional enhancers from activation of unrelated promoters. In vertebrates, insulator's function requires association with the CCCTC-binding factor (CTCF), a protein that recognizes long and diverse nucleotide sequences. While insulators are critical in gene regulation, only a few have been reported. Here, we describe 13,804 CTCF-binding sites in potential insulators of the human genome, discovered experimentally in primary human fibroblasts. Most of these sequences are located far from the transcriptional start sites, with their distribution strongly correlated with genes. The majority of them fit to a consensus motif highly conserved and suitable for predicting possible insulators driven by CTCF in other vertebrate genomes. In addition, CTCF localization is largely invariant across different cell types. Our results provide a resource for investigating insulator function and possible other general and evolutionarily conserved activities of CTCF sites.
Kim
Tae Hoon
TH
Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093-0653, USA. taehoon.kim@yale.edu
Abdullaev
Ziedulla K
ZK
Smith
Andrew D
AD
Ching
Keith A
KA
Loukinov
Dmitri I
DI
Green
Roland D
RD
Zhang
Michael Q
MQ
Lobanenkov
Victor V
VV
Ren
Bing
B
D000818:Animals; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D038101:Insulator Elements / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000378:metabolism*; D020298:U937 Cells; D014714:Vertebrates / Q000235:genetics
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; D012097:Repressor Proteins