transcriptional repressor CTCF; 11-zinc finger protein; CCCTC-binding factor; CTCFL paralog (CTCF)

Function

• chromatin binding factor
• binds to DNA sequence specific sites
• role in transcriptional regulation by binding to chromatin insulators & preventing interaction between promoter & nearby enhancers & silencers
• acts as transcriptional repressor binding to promoters of vertebrate MYC gene & BAG1 gene
• also binds to the PLK & PIM1 promoters
• acts as a transcriptional activator of APP
• regulates APOA1/C3/A4/A5 gene cluster & controls MHC class II gene expression
• role in oocyte & preimplantation embryo development by activating or repressing transcription
• seems to act as tumor suppressor
• role in the epigenetic regulation
• participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus
  • on the maternal allele, binding within the H19 imprinting control region (ICR) mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to IGF2
• role in gene silencing over considerable distances in the genome
• preferentially interacts with unmethylated DNA, preventing spreading of CpG methylation & maintaining methylation-free zones
• inversely, binding to target sites is prevented by CpG methylation
• role in chromatin remodeling
• can dimerize when it is bound to different DNA sequences, mediating long-range chromatin looping
• mediates interchromosomal association between IGF2/H19 & WSB1/NF1 & may direct distant DNA segments to a common transcription factory
• causes local loss of histone acetylation & gain of histone methylation in the beta-globin locus, without affecting transcription
• when bound to chromatin, it provides an anchor point for nucleosome positioning
• seems to be essential for homologous X-chromosome pairing
• may participate with Tsix in establishing a regulatable epigenetic switch for X chromosome inactivation
• may play a role in preventing the propagation of stable methylation at the escape genes from X-inactivation
• involved in sister chromatid cohesion
• associates with both centromeres & chromosomal arms during metaphase & required for cohesin localization to CTCF sites
• regulates asynchronous replication of IGF2/H19
• sumoylated on Lys-74 & Lys-689
• sumoylation of CTCF contributes to the repressive function of CTCF on the MYC P2 promoter (putative)
• interacts with CHD8

Structure

• the 11 Zn+2 fingers are highly conserved among vertebrates, exhibiting almost identical amino acid sequences
• different subsets or combination of individual Zn+2 fingers gives the ability to CTCF to recognize multiple DNA target sites
• belongs to the CTCF Zn+2-finger protein family
• contains 11 C2H2-type Zn+2 fingers

Compartment

• nucleus, nucleoplasm
• chromosome, centromere
• may translocate to the nucleolus upon cell differentiation
• associates with both centromeres & chromosomal arms during metaphase
• associates with the H19 ICR in mitotic chromosomes
• may be preferentially excluded from heterochromatin during interphase

Expression

• ubiquitous
• absent in primary spermatocytes

More general terms

• transcriptional silencer (transcriptional repressor)
• C2H2 type zinc finger protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=10664
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:10664
• OMIM: https://mirror.omim.org/entry/604167
• UniProt: http://www.uniprot.org/uniprot/P49711.html