CTCF

Domain

The 11 zinc fingers are highly conserved among vertebrates, exhibiting almost identical amino acid sequences. Different subsets or combination of individual zinc fingers gives the ability to CTCF to recognize multiple DNA target sites.

Function

Chromatin binding factor that binds to DNA sequence specific sites. Involved in transcriptional regulation by binding to chromatin insulators and preventing interaction between promoter and nearby enhancers and silencers. Acts as transcriptional repressor binding to promoters of vertebrate MYC gene and BAG1 gene. Also binds to the PLK and PIM1 promoters. Acts as a transcriptional activator of APP. Regulates APOA1/C3/A4/A5 gene cluster and controls MHC class II gene expression. Plays an essential role in oocyte and preimplantation embryo development by activating or repressing transcription. Seems to act as tumor suppressor. Plays a critical 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. Plays a critical role in gene silencing over considerable distances in the genome. Preferentially interacts with unmethylated DNA, preventing spreading of CpG methylation and maintaining methylation-free zones. Inversely, binding to target sites is prevented by CpG methylation. Plays an important 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 and WSB1/NF1 and may direct distant DNA segments to a common transcription factory. Causes local loss of histone acetylation and gain of histone methylation in the beta-globin locus, without affecting transcription. When bound to chromatin, it provides an anchor point for nucleosomes 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 and chromosomal arms during metaphase and required for cohesin localization to CTCF sites. Regulates asynchronous replication of IGF2/H19. Plays a role in the recruitment of CENPE to the pericentromeric/centromeric regions of the chromosome during mitosis (PubMed:26321640).

Involvement in disease

Mental retardation, autosomal dominant 21

MRD21

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Additional MRD21 features include short stature, microcephaly, and developmental delay.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Sumoylated on Lys-74 and Lys-689; sumoylation of CTCF contributes to the repressive function of CTCF on the MYC P2 promoter.

Sequence similarities

Belongs to the CTCF zinc-finger protein family.

Tissue specificity

Ubiquitous. Absent in primary spermatocytes.

Cellular localization

• Nucleus
• Nucleoplasm
• Chromosome
• Chromosome
• Centromere
• May translocate to the nucleolus upon cell differentiation. Associates with both centromeres and chromosomal arms during metaphase. Associates with the H19 ICR in mitotic chromosomes. May be preferentially excluded from heterochromatin during interphase.

Alternative names

• Transcriptional repressor CTCF
• 11-zinc finger protein
• CCCTC-binding factor
• CTCFL paralog
• CTCF

Database links

• entrezGene:10664
• omim:604167
• swissprot:P49711

Target type

Proteins

Primary research area

Epigenetics

Molecular weight

82785Da