CTCF (CCCTC-binding factor (zinc finger protein))

2013-05-01   Jacques Piette 

Institut de Genetique Moleculaire de Montpellier (CNRS-Universite de Montpellier I-II UMR5535), 1919 Route de Mende, 34293, Montpellier-Cedex 5, France


Atlas Image
Figure 1. Schematic representation of CTCF location on chromosome 16, gene structure and transcripts. Chromosome 16 is represented with the characteristic banding pattern. The region surrounding the CTCF gene is enlarged. Genes are represented by arrows pointing in the direction of transcription. Transcripts are represented with exons as vertical bars and introns as lines. Distances are in kilo bases (NCBI Map Viewer).



See figure 1.


76776 bp gene (Ensembl).


Ubiquitously highly expressed gene (GeneCards), 12 exons, 11 introns with at least 5 differentially spliced transcripts (Ensembl).




Atlas Image
Figure 2. Schematic representation of the CTCF protein. Protein sequences encoded by exons are boxed. 11 ring fingers are indicated by green boxes as also putative AT-hooks by blue boxes (Ensembl). The interaction domain with the SA2 subunit of cohesin is underlined in red (Xiao et al., 2011). Phosphorylated residues are in black (PhosphoSitePlus), those sensitive to rapamycin are indicated by R (Chen et al., 2009) and those phosphorylated by CKII by CKII (El-Kady and Klenova, 2005; Klenova et al., 2001), sumoylated residues are in red (Kitchen and Schoenherr, 2010; MacPherson et al., 2009), acetylated residue is indicated by Ac (Choudhary et al., 2009). The domain containing poly(ADPribosyl)ation sites (PAR) is boxed in red (Farrar et al., 2010), the NTP-binding site in blue and the NLS in purple. Residues mutated in tumors are indicated (see further), BT = breast tumor, PT = prostate tumor and WT = Wilms tumor.


CTCF was originally described as a c-myc activator (Klenova et al., 1993). It is a 727 aa protein with a MW of 82.8 kD, a charge of 8.5 and an iso electric point of 6.95 (Ensembl). The central domain with 11 zinc fingers of the C2H2 type is highly conserved.


CTCF is an abundant and ubiquitously expressed protein, yet absent in primary spermatocytes (Loukinov et al., 2002). It is downregulated during differentiation of human myeloid leukemia cells (Delgado et al., 1999; Torrano et al., 2005). Post-traductional modifications include acetylation (Choudhary et al., 2009), sumoylation (Kitchen and Schoenherr, 2010; MacPherson et al., 2009), which is regulated by hypoxic stress (Wang et al., 2012a), phosphorylation, in particular ser604-612 by CKII (El-Kady and Klenova, 2005; Klenova et al., 2001), and poly(ADPribo)sylation (see figure 2). The latter modification is lost or decreased in proliferating cells and in BT (Docquier et al., 2009) (for sites and role see Farrar et al., 2010; Yu et al., 2004; Guastafierro et al., 2013). CTCF is a downstream target protein of growth factor-induced pathways and is regulated by EGF and insulin through activation of ERK and AKT signaling cascades (Gao et al., 2007). It was recently shown to be regulated by NF-kB (Lu et al., 2010).


CTCF is localized in the nucleoplasm of proliferating cells with exclusion from the nucleolus. It was detected at the centrosomes and midbody during mitosis (Zhang et al., 2004). It is associated with the nuclear matrix (Dunn et al., 2003; Yusufzai and Felsenfeld, 2004) and the Lamina (Guelen et al., 2008; Ottaviani et al., 2009). Nucleolar translocation after growth arrest is accompanied by inhibition of nucleolar transcription (Torrano et al., 2006). Cytoplasmic expression was described in sporadic breast tumors (Rakha et al., 2004).


CTCF is an essential protein, since KO mice die before ED 9.5 (Heath et al., 2008) (reviewed in Filippova, 2008; Phillips and Corces, 2009). It interacts with numerous ubiquitous and cell-type specific genomic sites (Chen et al., 2008; Bao et al., 2008; Barski et al., 2007; Kim et al., 2007; Chen et al., 2012). The 11 Zn fingers would provide flexibility in DNA recognition (Filippova et al., 1996), the central 4 bind to a consensus DNA sequence (Filippova et al., 1998; Renda et al., 2007). Multiple interacting proteins were described including RNA polymerase II (Chernukhin et al., 2007), cohesin (Parelho et al., 2008; Rubio et al., 2008; Wendt et al., 2008; Xiao et al., 2011), Suz12 (Li et al., 2008), CHD8 (Ishihara et al., 2006), YY1 (Donohoe et al., 2007), nucleophosmin (Yusufzai et al., 2004), Kaiso (Defossez et al., 2005) and Sin3A (Lutz et al., 2000). XPG endonuclease promotes DNA breaks and DNA demethylation at promoters allowing the recruitment of CTCF and gene looping, which is further stabilized by XPF (Le May et al., 2012). By mediating intra and interchromosomal contacts through its interaction with cohesin, CTCF plays a central role in organization of topological domains inside the nucleus. Cell-type specific binding sites lead to specific interactomes and transcriptional programs (Hou et al., 2010; Handoko et al., 2011; Dixon et al., 2012; Botta et al., 2010; reviewed by Merkenschlager and Odom, 2013). The plasticity in binding sites occupancy is linked to DNA methylation (Wang et al., 2012b) and could depend also on CTCF interaction with other factors (see concept of modular insulators in Weth et al., 2010). One thoroughly studied factor is the thyroid receptor (Awad et al., 1999; Lutz et al., 2003). Its peculiar chromosomal environment could explain the multiple (not necessarily exclusive) functions that were described for CTCF, including chromatin barrier (Cuddapah et al., 2009; Witcher and Emerson, 2009), promoter insulation from enhancer (Bell et al., 1999) or silencer (Hou et al., 2008), transcriptional activation (Gombert and Krumm, 2009) (for instance of the tumour suppressor genes INK4A/ARF (Rodriguez et al., 2010) and p53 (Soto-Reyes and Recillas-Targa, 2010)), repression (for instance hTERT (Renaud et al., 2005)), nucleosome positioning (Fu et al., 2008b), protection from DNA methylation (Mukhopadhyay et al., 2004; Schoenherr et al., 2003; Guastafierro et al., 2008), preservation of triplet-repeat stability (Cho et al., 2005; Filippova et al., 2001; Libby et al., 2008), imprinting (Fedoriw et al., 2004; Fitzpatrick et al., 2007), X chromosome inactivation (Chao et al., 2002), chromosome "kissing" (Ling et al., 2006), transvection (Liu et al., 2008), death signaling (Docquier et al., 2005; Gomes and Espinosa, 2010; Li and Lu, 2007), replication timing (Bergstrom et al., 2007), mitotic bookmarking (Burke et al., 2005), MHC class II gene expression (Majumder et al., 2008), V(D)J recombination (Guo et al., 2011; reviewed by Chaumeil and Skok, 2012), miRNA expression (Saito and Saito, 2012), telomere end protection (Deng et al., 2012), neuronal diversity (Monahan et al., 2012), myogenesis (Delgado-Olguin et al., 2011), splicing (Shukla et al., 2011) and angiogenesis (Tang et al., 2011). Considering the central role of CTCF in transcriptional regulation, it is likely to play a role in adaptive evolution in Drosophila (Ni et al., 2012), and in the evolutionary succes of bilateria (Heger et al., 2012). Remodeling of CTCF binding sites and the accompanying interactome during evolution could be driven by retrotransposon expansion (Schmidt et al., 2012).


49 orthologues were described including D. melanogaster (Smith et al., 2009) and C. elegans proteins (Moon et al., 2005), 3 paralogues: CTCFL or BORIS, originating from a gene duplication in reptiles (Hore et al., 2008; Loukinov et al., 2002), and possibly ZFP64 (Mack et al., 1997) and the Histone H4 transcription factor HINF-P (van Wijnen et al., 1991).



SNP at AA 630 /K /E 90 /D /G 447 fR (NCBI).


Non-coding mutations only.


Mutations are rare and include point mutations of Zn-fingers in breast (BT) (Aulmann et al., 2003), prostate (PT) and Wilms tumor (WT) (Filippova et al., 2002; Tiffen et al., 2013), insertion in BT (Aulmann et al., 2003) (see figure 2), and indels in AML (Dolnik et al., 2012).

Implicated in

Entity name
Various cancers
There is evidence for a tumor-suppressor role of CTCF (reviewed in Fiorentino and Giordano, 2012). LOH of CTCF was described in many cancers together with potential tumor suppressor genes (TSG), including E-Cad, since it is part of a larger deletion (Cancer Chromosomes; Sanger institute). In addition to WT (Yeh et al., 2002; Mummert et al., 2005), BT (Rakha et al., 2004), PT (Filippova et al., 1998), LOH was found in laryngeal squamous cell carcinoma (Grbesa et al., 2008), however, there is no evidence that CTCF is the TSG at 16q22.1 (Rakha et al., 2005), except possibly in lobular carcinoma in situ of the breast (Green et al., 2009). CTCF was also described to be overexpressed in BT (Docquier et al., 2005). An indirect role of CTCF in tumor progression is mainly suggested by mutation or aberrant methylation of its bindings sites (reviewed by Recillas-Targa et al., 2006). Interestingly, a causal link between LOH of CTCF and hypermethylation was proposed by Mummert et al. in 2005, although no real correlation was found by Yeh et al. in 2002. Methylation of CTCF sites was first described in the IGF2 imprinting control region in WT (Cui et al., 2001). Aberrant methylation of this region was also found in PT (Fu et al., 2008a; Paradowska et al., 2009), HNSCC (De Castro Valente Esteves et al., 2006; Esteves et al., 2005), colorectal cancer (Nakagawa et al., 2001), osteosarcoma (Ulaner et al., 2003), ovarian carcinoma (Dammann et al., 2010) and laryngeal squamous cell carcinoma (Grbesa et al., 2008). Hypomethylation was described in bladder cancer (Takai et al., 2001). YY1 binds with CTCF to a hypomethylated form of the macrosatellite DXZ4 on the inactive X chromosome in some male carcinomas (Moseley et al., 2012). Microdeletions were described in Beckwith-Wiedemann syndrome and WT (Prawitt et al., 2005; Sparago et al., 2007; Beygo et al., 2013). Other methylated CTCF targets were found in the genes AWT1 or WT1-AS in WT (Hancock et al., 2007), Bcl6 in B cell lymphomas (Lai et al., 2010), the miR125b locus in breast cancer (Soto-Reyes et al., 2012), p53, pRb (De La Rosa-Velazquez et al., 2007; Davalos-Salas et al., 2011), ARF (Tam et al., 2003; Rodriguez et al., 2010), INK4B, BRCA1 (Butcher et al., 2004; Butcher and Rodenhiser, 2007; Xu et al., 2010) and Rasgrf1 (Yoon et al., 2005). CTCF and its paralogue BORIS regulate pRb in lung cancer (Fiorentino et al., 2011), and CTCF could regulate the response to oestrogen in breast cancer (Zhang et al., 2010).
We describe below the rare cases of point mutations affecting the CTCF protein.
Entity name
Invasive ductal breast carcinoma, grade 2
G2 grade tumor, no protein detected (Aulmann et al., 2003).
14 bp insertion at AA D91, see figure 2.
Entity name
Invasive ductal breast carcinoma, grade 3
G3 grade tumor (Aulmann et al., 2003).
LOH and Q72H, figure 2.
Entity name
Breast cancer
Zinc finger mutation (Filippova et al., 2002).
LOH and K343E, figure 2.
Entity name
Prostate cancer
Zinc finger mutation (Filippova et al., 2002).
LOH and H344E, figure 2.
Entity name
Wilms tumor
Zinc finger mutation (Filippova et al., 2002).
LOH and R339W or R448Q, figure 2.
Entity name
(Dolnik et al., 2012).


Pubmed IDLast YearTitleAuthors
145038072003CTCF gene mutations in invasive ductal breast cancer.Aulmann S et al
104809231999Negative transcriptional regulation mediated by thyroid hormone response element 144 requires binding of the multivalent factor CTCF to a novel target DNA sequence.Awad TA et al
179818432008CTCFBSDB: a CTCF-binding site database for characterization of vertebrate genomic insulators.Bao L et al
175124142007High-resolution profiling of histone methylations in the human genome.Barski A et al
104586131999The protein CTCF is required for the enhancer blocking activity of vertebrate insulators.Bell AC et al
173299682007CTCF regulates asynchronous replication of the imprinted H19/Igf2 domain.Bergström R et al
231183522013The molecular function and clinical phenotype of partial deletions of the IGF2/H19 imprinting control region depends on the spatial arrangement of the remaining CTCF-binding sites.Beygo J et al
210458202010Intra- and inter-chromosomal interactions correlate with CTCF binding genome wide.Botta M et al
161078752005CTCF binding and higher order chromatin structure of the H19 locus are maintained in mitotic chromatin.Burke LJ et al
170710742007Epigenetic inactivation of BRCA1 is associated with aberrant expression of CTCF and DNA methyltransferase (DNMT3B) in some sporadic breast tumours.Butcher DT et al
117431582002CTCF, a candidate trans-acting factor for X-inactivation choice.Chao W et al
224246102012The role of CTCF in regulating V(D)J recombination.Chaumeil J et al
228299472012Comprehensive identification and annotation of cell type-specific and ubiquitous CTCF-binding sites in the human genome.Chen H et al
192763682009CDC25B mediates rapamycin-induced oncogenic responses in cancer cells.Chen RQ et al
185557852008Integration of external signaling pathways with the core transcriptional network in embryonic stem cells.Chen X et al
172106452007CTCF interacts with and recruits the largest subunit of RNA polymerase II to CTCF target sites genome-wide.Chernukhin I et al
162859292005Antisense transcription and heterochromatin at the DM1 CTG repeats are constrained by CTCF.Cho DH et al
196088612009Lysine acetylation targets protein complexes and co-regulates major cellular functions.Choudhary C et al
190566952009Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains.Cuddapah S et al
114313212001Loss of imprinting of insulin-like growth factor-II in Wilms' tumor commonly involves altered methylation but not mutations of CTCF or its binding site.Cui H et al
199568462010Frequent aberrant methylation of the imprinted IGF2/H19 locus and LINE1 hypomethylation in ovarian carcinoma.Dammann RH et al
216636592011Gain of DNA methylation is enhanced in the absence of CTCF at the human retinoblastoma gene promoter.Dávalos-Salas M et al
163918432006H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: a pilot case-control analysis.De Castro Valente Esteves LI et al
173635762007Epigenetic regulation of the human retinoblastoma tumor suppressor gene promoter by CTCF.De La Rosa-Velázquez IA et al
162303452005The human enhancer blocker CTC-binding factor interacts with the transcription factor Kaiso.Defossez PA et al
100371381999Differential expression and phosphorylation of CTCF, a c-myc transcriptional regulator, during differentiation of human myeloid cells.Delgado MD et al
212889052011CTCF promotes muscle differentiation by modulating the activity of myogenic regulatory factors.Delgado-Olguín P et al
230107782012A role for CTCF and cohesin in subtelomere chromatin organization, TERRA transcription, and telomere end protection.Deng Z et al
224953002012Topological domains in mammalian genomes identified by analysis of chromatin interactions.Dixon JR et al
197379642009Decreased poly(ADP-ribosyl)ation of CTCF, a transcription factor, is associated with breast cancer phenotype and cell proliferation.Docquier F et al
229769562012Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing.Dolnik A et al
172182702007Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch.Donohoe ME et al
128781732003The insulator binding protein CTCF associates with the nuclear matrix.Dunn KL et al
157338522005Regulation of the transcription factor, CTCF, by phosphorylation with protein kinase CK2.El-Kady A et al
160156662005DNA methylation in the CTCF-binding site I and the expression pattern of the H19 gene: does positive expression predict poor prognosis in early stage head and neck carcinomas?Esteves LI et al
200385292010Mutational analysis of the poly(ADP-ribosyl)ation sites of the transcription factor CTCF provides an insight into the mechanism of its regulation by poly(ADP-ribosyl)ation.Farrar D et al
147160172004Transgenic RNAi reveals essential function for CTCF in H19 gene imprinting.Fedoriw AM et al
179503792008Genetics and epigenetics of the multifunctional protein CTCF.Filippova GN et al
214654782012The tumor suppressor role of CTCF.Fiorentino FP et al
172421892007Allele-specific binding of CTCF to the multipartite imprinting control region KvDMR1.Fitzpatrick GV et al
187015052008Aging and cancer-related loss of insulin-like growth factor 2 imprinting in the mouse and human prostate.Fu VX et al
186546292008The insulator binding protein CTCF positions 20 nucleosomes around its binding sites across the human genome.Fu Y et al
180211712007Functional role of CCCTC binding factor in insulin-stimulated cell proliferation.Gao J et al
195684262009Targeted deletion of multiple CTCF-binding elements in the human C-MYC gene reveals a requirement for CTCF in C-MYC expression.Gombert WM et al
204789952010Gene-specific repression of the p53 target gene PUMA via intragenic CTCF-Cohesin binding.Gomes NP et al
186045142008Loss of imprinting of IGF2 and H19, loss of heterozygosity of IGF2R and CTCF, and Helicobacter pylori infection in laryngeal squamous cell carcinoma.Grbesa I et al
182134752009Loss of expression of chromosome 16q genes DPEP1 and CTCF in lobular carcinoma in situ of the breast.Green AR et al
231161802013ADP-ribose polymer depletion leads to nuclear Ctcf re-localization and chromatin rearrangement(1).Guastafierro T et al
184636342008Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions.Guelen L et al
219091132011CTCF-binding elements mediate control of V(D)J recombination.Guo C et al
172106702007A CTCF-binding silencer regulates the imprinted genes AWT1 and WT1-AS and exhibits sequential epigenetic defects during Wilms' tumourigenesis.Hancock AL et al
216859132011CTCF-mediated functional chromatin interactome in pluripotent cells.Handoko L et al
189234232008CTCF regulates cell cycle progression of alphabeta T cells in the thymus.Heath H et al
230456512012The chromatin insulator CTCF and the emergence of metazoan diversity.Heger P et al
187697112008The evolution of epigenetic regulators CTCF and BORIS/CTCFL in amniotes.Hore TA et al
201336002010Cell type specificity of chromatin organization mediated by CTCF and cohesin.Hou C et al
190742632008CTCF-dependent enhancer-blocking by alternative chromatin loop formation.Hou C et al
169493682006CTCF-dependent chromatin insulator is linked to epigenetic remodeling.Ishihara K et al
173828892007Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome.Kim TH et al
205897582010Sumoylation modulates a domain in CTCF that activates transcription and decondenses chromatin.Kitchen NS et al
112389552001Functional phosphorylation sites in the C-terminal region of the multivalent multifunctional transcriptional factor CTCF.Klenova EM et al
207330342010DNA methylation prevents CTCF-mediated silencing of the oncogene BCL6 in B cell lymphomas.Lai AY et al
227711162012XPG and XPF endonucleases trigger chromatin looping and DNA demethylation for accurate expression of activated genes.Le May N et al
186629932008CTCF regulates allelic expression of Igf2 by orchestrating a promoter-polycomb repressive complex 2 intrachromosomal loop.Li T et al
175836942007Functional role of CCCTC binding factor (CTCF) in stress-induced apoptosis.Li T et al
190089402008CTCF cis-regulates trinucleotide repeat instability in an epigenetic manner: a novel basis for mutational hot spot determination.Libby RT et al
166142242006CTCF mediates interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1.Ling JQ et al
186257442008Transvection mediated by the translocated cyclin D1 locus in mantle cell lymphoma.Liu H et al
120114412002BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma.Loukinov DI et al
201103622010NF-kappaB subtypes regulate CCCTC binding factor affecting corneal epithelial cell fate.Lu L et al
126601642003Thyroid hormone-regulated enhancer blocking: cooperation of CTCF and thyroid hormone receptor.Lutz M et al
190292522009The CTCF insulator protein is posttranslationally modified by SUMO.MacPherson MJ et al
90343071997A search for a mammalian homologue of the Drosophila photoreceptor development gene glass yields Zfp64, a zinc finger encoding gene which maps to the distal end of mouse chromosome 2.Mack HG et al
183471002008The insulator factor CTCF controls MHC class II gene expression and is required for the formation of long-distance chromatin interactions.Majumder P et al
234989372013CTCF and cohesin: linking gene regulatory elements with their targets.Merkenschlager M et al
225501782012Role of CCCTC binding factor (CTCF) and cohesin in the generation of single-cell diversity of protocadherin-α gene expression.Monahan K et al
156781592005CTCF is conserved from Drosophila to humans and confers enhancer blocking of the Fab-8 insulator.Moon H et al
220648602012YY1 associates with the macrosatellite DXZ4 on the inactive X chromosome and binds with CTCF to a hypomethylated form in some male carcinomas.Moseley SC et al
152565112004The binding sites for the chromatin insulator protein CTCF map to DNA methylation-free domains genome-wide.Mukhopadhyay R et al
157618652005Association of chromosome arm 16q loss with loss of imprinting of insulin-like growth factor-II in Wilms tumor.Mummert SK et al
111208912001Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19-associated CTCF-binding sites in colorectal cancer.Nakagawa H et al
231396402012Adaptive evolution and the birth of CTCF binding sites in the Drosophila genome.Ni X et al
196444482009Identification of a perinuclear positioning element in human subtelomeres that requires A-type lamins and CTCF.Ottaviani A et al
195135552009Aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia.Paradowska A et al
182377722008Cohesins functionally associate with CTCF on mammalian chromosome arms.Parelho V et al
195637532009CTCF: master weaver of the genome.Phillips JE et al
157439162005Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith-Wiedemann syndrome and Wilms' tumor.Prawitt D et al
156093122005High-resolution analysis of 16q22.1 in breast carcinoma using DNA amplifiable probes (multiplex amplifiable probe hybridization technique) and immunohistochemistry.Rakha EA et al
153542172004Expression of the transcription factor CTCF in invasive breast cancer: a candidate gene located at 16q22.1.Rakha EA et al
169897202006Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection and its role in carcinogenesis.Recillas-Targa F et al
163268642005CTCF binds the proximal exonic region of hTERT and inhibits its transcription.Renaud S et al
178274992007Critical DNA binding interactions of the insulator protein CTCF: a small number of zinc fingers mediate strong binding, and a single finger-DNA interaction controls binding at imprinted loci.Renda M et al
200512282010CTCF is a DNA methylation-sensitive positive regulator of the INK/ARF locus.Rodriguez C et al
185508112008CTCF physically links cohesin to chromatin.Rubio ED et al
230560062012Role of CTCF in the regulation of microRNA expression.Saito Y et al
222444522012Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages.Schmidt D et al
124615252003CTCF maintains differential methylation at the Igf2/H19 locus.Schoenherr CJ et al
219643342011CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.Shukla S et al
192109642009Genome wide ChIP-chip analyses reveal important roles for CTCF in Drosophila genome organization.Smith ST et al
222771292012Disruption of CTCF at the miR-125b1 locus in gynecological cancers.Soto-Reyes E et al
171588212007Mechanisms causing imprinting defects in familial Beckwith-Wiedemann syndrome with Wilms' tumour.Sparago A et al
169512512006CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus.Splinter E et al
117265482001Large scale mapping of methylcytosines in CTCF-binding sites in the human H19 promoter and aberrant hypomethylation in human bladder cancer.Takai D et al
125383572003Perturbations of the Ink4a/Arf gene locus in aflatoxin B1-induced mouse lung tumors.Tam AS et al
218967592011Restraint of angiogenesis by zinc finger transcription factor CTCF-dependent chromatin insulation.Tang M et al
235530992013The cancer-testis antigen BORIS phenocopies the tumor suppressor CTCF in normal and neoplastic cells.Tiffen JC et al
159417182005CTCF regulates growth and erythroid differentiation of human myeloid leukemia cells.Torrano V et al
165955482006Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism.Torrano V et al
125888012003Loss of imprinting of IGF2 and H19 in osteosarcoma is accompanied by reciprocal methylation changes of a CTCF-binding site.Ulaner GA et al
229559802012Widespread plasticity in CTCF occupancy linked to DNA methylation.Wang H et al
223549642012De-SUMOylation of CCCTC binding factor (CTCF) in hypoxic stress-induced human corneal epithelial cells.Wang J et al
182354442008Cohesin mediates transcriptional insulation by CCCTC-binding factor.Wendt KS et al
204049252010Modular insulators: genome wide search for composite CTCF/thyroid hormone receptor binding sites.Weth O et al
194505262009Epigenetic silencing of the p16(INK4a) tumor suppressor is associated with loss of CTCF binding and a chromatin boundary.Witcher M et al
214447192011Specific sites in the C terminus of CTCF interact with the SA2 subunit of the cohesin complex and are required for cohesin-dependent insulation activity.Xiao T et al
194665412010CpG island methylation affects accessibility of the proximal BRCA1 promoter to transcription factors.Xu J et al
122037792002Chromosome arm 16q in Wilms tumors: unbalanced chromosomal translocations, loss of heterozygosity, and assessment of the CTCF gene.Yeh A et al
163145372005Rasgrf1 imprinting is regulated by a CTCF-dependent methylation-sensitive enhancer blocker.Yoon B et al
153618752004Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation.Yu W et al
147593732004CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species.Yusufzai TM et al
149805042004Dynamic association of the mammalian insulator protein CTCF with centrosomes and the midbody.Zhang R et al
206103842010CCCTC-binding factor acts upstream of FOXA1 and demarcates the genomic response to estrogen.Zhang Y et al
150842422004A screen for germline mutations in the gene encoding CCCTC-binding factor (CTCF) in familial non-BRCA1/BRCA2 breast cancer.Zhou XL et al
231932942013CTCFBSDB 2.0: a database for CTCF-binding sites and genome organization.Ziebarth JD et al
16558211991Transcriptional element H4-site II of cell cycle regulated human H4 histone genes is a multipartite protein/DNA interaction site for factors HiNF-D, HiNF-M, and HiNF-P: involvement of phosphorylation.van Wijnen AJ et al

Other Information

Locus ID:

NCBI: 10664
MIM: 604167
HGNC: 13723
Ensembl: ENSG00000102974


dbSNP: 10664
ClinVar: 10664
TCGA: ENSG00000102974


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Developmental BiologyREACTOMER-HSA-1266738
Activation of HOX genes during differentiationREACTOMER-HSA-5619507
Activation of anterior HOX genes in hindbrain development during early embryogenesisREACTOMER-HSA-5617472

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
182354442008Cohesin mediates transcriptional insulation by CCCTC-binding factor.522
173828892007Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome.519
219643342011CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.413
182377722008Cohesins functionally associate with CTCF on mammalian chromosome arms.410
190609112009Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.392
246143162014CTCF: an architectural protein bridging genome topology and function.370
190566952009Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains.333
266866512015CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription.292
243358032014Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells.275
262766362015CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function.262


Jacques Piette

CTCF (CCCTC-binding factor (zinc finger protein))

Atlas Genet Cytogenet Oncol Haematol. 2013-05-01

Online version: http://atlasgeneticsoncology.org/gene/40187/ctcf

Historical Card

2011-04-01 CTCF (CCCTC-binding factor (zinc finger protein)) by  Jacques Piette 

Institut de Genetique Moleculaire de Montpellier (CNRS-Universite de Montpellier I-II UMR5535), 1919 Route de Mende, 34293, Montpellier-Cedex 5, France