Entrez Gene

General information | Expression | Regulation | Mutation | Interaction

Basic Information
Gene ID	10664
Name	CTCF
Synonymous	-;CCCTC-binding factor (zinc finger protein);CTCF;CCCTC-binding factor (zinc finger protein)
Definition	11 zinc finger transcriptional repressor\|11-zinc finger protein\|CTCFL paralog\|transcriptional repressor CTCF
Position	16q21-q22.3
Gene type	protein-coding
Source	Count: 2; Generif,UniProt
Sentence	Abstract
Results substantiate the critical role of CTCF in establishing and maintaining p16INK4A and other tumor suppressor genes in higher-order chromosomal domains through appropriate boundary formation.	The p16(INK4a) tumor suppressor gene is a frequent target of epigenetic inactivation in human cancers, which is an early event in breast carcinogenesis. We describe the existence of a chromatin boundary upstream of the p16 gene that is lost when this gene is aberrantly silenced. We show that the multifunctional protein CTCF associates in the vicinity of this boundary and absence of binding strongly coincides with p16 silencing in multiple types of cancer cells. CTCF binding also correlates with RASSF1A and CDH1 gene activation, and CTCF interaction is absent when these genes are methylated and silenced. Interestingly, defective poly(ADP-ribosyl)ation of CTCF and dissociation from the molecular chaperone Nucleolin occur in p16-silenced cells, abrogating its proper function. Thus, destabilization of specific chromosomal boundaries through aberrant crosstalk between CTCF, poly(ADP-ribosyl)ation, and DNA methylation may be a general mechanism to inactivate tumor suppressor genes and initiate tumorigenesis in numerous forms of human cancers.
"observations suggest that CTCF may represent a novel tumor suppressor gene that displays tumor-specific ""change of function"" rather than complete ""loss of function"""	CTCF is a widely expressed 11-zinc finger (ZF) transcription factor that is involved in different aspects of gene regulation including promoter activation or repression, hormone-responsive gene silencing, methylation-dependent chromatin insulation, and genomic imprinting. Because CTCF targets include oncogenes and tumor suppressor genes, we screened over 100 human tumor samples for mutations that might disrupt CTCF activity. We did not observe any CTCF mutations leading to truncations/premature stops. Rather, in breast, prostate, and Wilms' tumors, we observed four different CTCF somatic missense mutations involving amino acids within the ZF domain. Each ZF mutation abrogated CTCF binding to a subset of target sites within the promoters/insulators of certain genes involved in regulating cell proliferation but did not alter binding to the regulatory sequences of other genes. These observations suggest that CTCF may represent a novel tumor suppressor gene that displays tumor-specific "change of function" rather than complete "loss of function."