Transcriptional repressor CTCF
Also known as: CTCF
Function
Chromatin binding factor that binds to DNA sequence specific sites and regulates the 3D structure of chromatin. Binds together strands of DNA, thus forming chromatin loops, and anchors DNA to cellular structures, such as the nuclear lamina. Defines the boundaries between active and heterochromatic DNA via binding to chromatin insulators, thereby preventing interaction between promoter and nearby enhancers and silencers. 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 (By similarity). Mediates interchromosomal association between IGF2/H19 and WSB1/NF1 and may direct distant DNA segments to a common transcription factory (By similarity). Regulates asynchronous replication of IGF2/H19 (By similarity). Plays a critical role in gene silencing over considerable distances in the genome (By similarity). 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. 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 (By similarity). 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. Plays a role in the recruitment of CENPE to the pericentromeric/centromeric regions of the chromosome during mitosis. Acts as a 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 (By similarity). Seems to act as tumor suppressor.
Classification
- Family (Pfam)
- PF00096 zf-C2H2, PF23611 zf-C2H2_16
- InterPro
- Zinc_finger, Znf-C2H2_CTCF, Znf_C2H2_sf, Znf_C2H2_type
- Functional cluster
- RNA-Polymerase II Transcription Factors
Experimental structures · PDB · 21
- 1X6H NMR
- 2CT1 NMR
- 5K5H X-ray 3.11A
- 5K5I X-ray 2.19A
- 5K5J X-ray 2.29A
- 5K5L X-ray 3.12A
- 5KKQ X-ray 1.74A
- 5T00 X-ray 2.19A
- 5T0U X-ray 3.20A
- 5UND X-ray 2.55A
- 5YEF X-ray 2.81A
- 5YEG X-ray 2.00A
- … and 9 more
A predicted model is available from AlphaFold.
Gene Ontology · 29
- GO:0000775 chromosome, centromeric region
- GO:0000793 condensed chromosome
- GO:0005730 nucleolus
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0043035 chromatin insulator sequence binding
- GO:0140587 chromatin loop anchoring activity
- GO:0003700 DNA-binding transcription factor activity
- GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific
- GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
- GO:0043565 sequence-specific DNA binding
- GO:0000976 transcription cis-regulatory region binding
- GO:0001221 transcription coregulator binding
- GO:0008270 zinc ion binding
- GO:0140588 chromatin looping
- GO:0007059 chromosome segregation
- GO:0006351 DNA-templated transcription
- GO:0040029 epigenetic regulation of gene expression
- GO:0071514 genomic imprinting
- GO:0008285 negative regulation of cell population proliferation
- GO:0045892 negative regulation of DNA-templated transcription
- GO:0010629 negative regulation of gene expression
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0045893 positive regulation of DNA-templated transcription
- GO:0010628 positive regulation of gene expression
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0071459 protein localization to chromosome, centromeric region
- GO:0070602 regulation of centromeric sister chromatid cohesion
- GO:0006357 regulation of transcription by RNA polymerase II
Disease associations
- CTCF-related neurodevelopmental disorder MONDO:0014213
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Transcriptional repressor CTCF 1.00
- Transcriptional repressor CTCF 1.00
- Transcriptional repressor CTCF 0.99
- PR domain zinc finger protein 15 0.85
- Transcription factor YY2 0.83
- Transcription factor E4F1 0.82
- Protein suppressor of hairy wing 0.82
- Transcription factor YY2 0.80
- Transcription factor YY2 0.80
- Zinc finger X-chromosomal protein 0.79
- Zinc finger protein su(Hw) 0.79
- Zinc finger protein 652 0.79
Co-cited proteins · studied together in the literature
- Transcriptional repressor CTCF 3 shared papers
- Transcriptional repressor CTCFL 2 shared papers
- Centromere-associated protein E 1 shared papers
- ATP-dependent chromatin remodeler CHD8 1 shared papers
- ATP-dependent chromatin remodeler CHD8 1 shared papers
- DNA (cytosine-5)-methyltransferase 3B 1 shared papers
- DNA (cytosine-5)-methyltransferase 1 1 shared papers
Literature · 30 cited papers
- CTCF genetic alterations in endometrial carcinoma are pro-tumorigenic. Oncogene · 2017
- Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
- CTCF recruits centromeric protein CENP-E to the pericentromeric/centromeric regions of chromosomes through unusual CTCF-binding sites. Cell Rep. · 2015
- Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
- De novo mutations in the genome organizer CTCF cause intellectual disability. Am. J. Hum. Genet. · 2013
- N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
- Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
- Architectural roles of multiple chromatin insulators at the human apolipoprotein gene cluster. EMBO J. · 2009
- … and 18 more in the literature graph