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Symbol CTCF contributors: mct/ - updated : 17-09-2017
HGNC name CCCTC-binding factor (zinc finger protein)
HGNC id 13723
Corresponding disease
MRD21 mental retardation, autosomal dominant 21
Location 16q22.1      Physical location : 67.596.309 - 67.673.087
Synonym name
  • multivalent zinc finger protein
  • chromatin insulator protein
  • Myc regulatory factor
  • 11 zinc finger transcriptional repressor
  • CTCFL paralog
  • DNA
    TYPE functioning gene
    STRUCTURE 76.78 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • promoter-proximal CTCF binding is significantly associated with RNA polymerase II pausing
  • MAPPING cloned Y linked N status provisional
    Map cen - FRA16B - D16S265 - D16S186 - [D16S347 - D16S398 - D16S4 - D16S318 - D16S301 - D16S421 ] - LCAT LCAT - CDH3 ,CDH1 - D16S496 - ALDOA ALDOA - D16S522 - D16S153 - qter
    regionally located located in the chromosomal region deleted in breast and prostate sporadic carcinomas (see TSG16A)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 3946 - 727 - 1999 10458613
    10 - 2985 - 399 - -
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
     vessel   lowly
    Digestiveesophagus   highly
     intestinesmall intestine  lowly
    Endocrineparathyroid   highly
     thyroid   highly
    Lymphoid/Immunethymus   highly
    Nervousbrain   highly
     nerve   lowly
    Reproductivefemale systembreastmammary gland lowly
     male systemtestis  highly
    Respiratoryrespiratory tractlarynx  lowly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Connectivebone  highly
    cell lineage cells of multiple lineages
    cell lines
    at STAGE
  • a short repression motif to residues 150-170 within the N-terminal domain
  • a eleven zinc finger domain
  • two transcription repressor domains
  • unstructured terminal segments of CTCF and CTCFL that could recruit different binding partners to chromosomes
  • CTCF loops can feature as domain barriers by demarcating nuclear lamin–chromatin interactions and delineating the chromosomes' subnuclear localizations
  • specific sites on the C-terminus of CTCF are essential for cohesin binding and insulator function , a RRGR motif is a putative nucleolar localization sequence in the C-terminal region of CTCF and is required for activating rRNA gene transcription
    interspecies homolog to rattus Ctcf (99.17 pc)
    homolog to murine Ctcf (99.04 pc)
    intraspecies paralog to CTCFL
  • CTCF zinc-finger protein family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
  • CTCF is widely distributed within the nucleus
  • basic FUNCTION
  • DNA-binding protein that plays essential roles in regulating genome activity through its capacity to act as an enhancer blocker
  • required for the enhancer blocking activity of vertebrate insulators (DNA sequence that can act as a barrier to the influences of neighboring cis-acting elements, preventing gene activation)
  • binding to imprinting control region (ICR) to maintain but not establish the differential methylation of ICR
  • putative trans-acting factor for X-inactivation choice, maybe together with TSIX
  • having insulator function (regulating access of enhancers to promoters) and protecting regions from DNA methylation
  • involved in transcriptional activation, insulation and genomic imprinting, but also in transcriptional repression
  • mediating interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1
  • playing a role in gene silencing or activation, chromatin insulation and genomic imprinting
  • participates in key cellular mechanisms underlying immortality by regulating TERT gene expression
  • largely determines the localization of cohesins (cohesin recruitment by CTCF provides a mechanism for the selective positioning of cohesins on chromosome arms)
  • involved in imprinting, long-range chromatin interactions and transcription
  • positively regulates cell growth in rapidly dividing thymocytes so that appropriate number of cells are generated before positive and negative selection in the thymus
  • important protein involved in chromatin organization and the epigenetic regulation of gene expression
  • multifunctional protein that involves regulation of growth factor- and cytokine-induced cell proliferation/differentiation
  • down stream target of stress-induced signaling cascades and it plays a significant anti-apoptotic role in regulation of stress-induced cellular responses in corneal epithelial and hematopoietic myeloid cells
  • master organizer of domain-wide allele-specific chromatin at the H19/Igf2 imprinted region
  • organizes transcription and chromatin in the three-dimensional space of the nucleus
  • with other sequence-specific DNA binding factors, recruits cohesin to specific chromosomal locations
  • role for CTCF in mediating chromatin loops, presumably different chromatin loops than those that involve ESR1 and FOXA1 during estrogen-mediated transcription in breast cancer cells
  • stimulates muscle gene expression by favoring MYOD1 recruitment
  • regulates Wnt signaling, linking CTCF to broad aspects of development
  • plays an important role in insulation and in large-scale organization of chromatin within the eukaryotic nucleus, that depends for both activities on recruitment of the cohesin complex
  • most characterized insulator-binding protein, implicated as a key genome organizer
  • enhancer bridging' activity that could potentially engage CTCF in generating cell-specific chromatin interactions and guide gene expression programs
  • unappreciated role for CTCF and cohesins in the repression of imprinted genes in somatic cells
  • CTCF-dependent chromatin insulation plays a pivotal role in governing physiological vascular growth
  • negatively regulates tumor angiogenesis
  • governs normal vascular formation in the developing retina, and depletion of CTCF causes excess intraretinal neovascularization
  • CTCF is a master regulator of genome spatial organization, and mediates the ubiquitous chromatin loops within the genome
  • functions as a switch-like molecule between the insulin signaling and the regulations of PAX6 and glucagon expression in pancreatic islet alpha-cells
  • CTCF and cohesin are integral components of most human subtelomeres, and important for the regulation of TERRA transcription and telomere end protection
  • potentially required for enhancer-driven gene activation and genomic interaction of enhancers and their regulated gene promoters in development
  • has a complex role in regulating FMR1 expression, probably through the organization of chromatin loops between sense/antisense transcriptional regulatory regions, as suggested by bioinformatics analysis
  • constitutive CTCF sites may play a role in organizing/maintaining the recently identified topological domains that are common across most human cells
  • crucial regulator of long-range chromatin interactions and coordinates specific communication between transcription factors and gene expression processes
  • novel role of CTCF and cohesin as regulators of transcriptional direction
  • role of CTCF in stabilizing long-range interactions between chromatin sites essential for maintaining nuclear architecture
  • CELLULAR PROCESS nucleotide, transcription, regulation
    a component
  • RNA polymerase 2 transcription factors
  • DDX5 and its associated noncoding RNA, steroid receptor RNA activator (SRA1), form a complex with CTCF that is essential for insulator function
  • might participate in a wide variety of differentiation and developmental programs in myogenesis that are, at least in part, regulated by Wnt signaling
  • enhancer bridging' activity could potentially engage CTCF in generating cell-specific chromatin interactions and guide gene expression programs
  • is a ubiquitous epigenetic regulator that has been proposed as a master keeper of chromatin organisation
    DNA DNA binding including most ICRs and many CpG islands
    RNA binding to H19
    small molecule
  • binding to imprinting control region (ICR)
  • specific binding partner of ZBTB33 (interaction occurs through a C-terminal region of CTCF and the POZ domain of ZBTB33, interaction that negatively regulates CTCF insulator activity)
  • interacting with CHD8 (interacts with the SNF2-like chromodomain helicase protein CHD8 and both are required for enhancer blocking activity and insulator function)
  • specifically binds to the 5 prime end of D4Z4 (is required for the insulation activity of D4Z4 but it does not appear to be sufficient)
  • recruits the cohesin complex to insulator sites and cohesin is required for insulator activity
  • direct interaction between CTCF and MYOD1 (CTCF is necessary for recruitment of MYOD1 to at least some of its target promoters and for muscle-specific gene expression activation)
  • interaction of CTCF with the cohesin complex involves direct contacts between the cohesin subunit STAG2 and specific regions of the C-terminal tail of CTCF
  • CTCF interactions harbor specific chromatin domains (CTCF interactions demarcate chromatin-nuclear membrane attachments and influence proper gene expression through extensive cross-talk between promoters and regulatory elements)
  • binds to multiple imprinted loci and is required for proper imprinted expression at the H19/Igf2 locus
  • interacting with CTCF (transcription of MGAT5B is mediated by the binding of CTCF)
  • binds to the proximal promoter of VEGFA (acts as an enhancer blocker to ensure appropriately confined VEGFA induction)
  • may be a master organizer in mediating the spatial organization of the KCNQ5 gene locus
  • associates with the distal ends and internal sites of the co-regulated 160 kb NANOG-DPPA3-GDF3 locus
  • partnership between CTCF and cohesin is emerging as a novel and perhaps pivotal aspect of gene regulatory mechanisms, in addition to playing a role in the organization of higher order chromatin architecture
  • may also play a key role in the pluripotency of cells through the regulation of MIR290 cluster
  • regulates the expression of IPO13, which, in turn, mediates the nuclear import of CTCF
  • NIPBL and cohesin have been reported to affect long-range chromosomal interactions, both independently and through interactions with CTCF
  • condensin competes with CTCF in binding to a specific rDNA locus and negatively regulates CTCF-mediated rRNA gene transcription
  • CTCF has a complex role in regulating FMR1 expression, probably through the organization of chromatin loops between sense/antisense transcriptional regulatory regions
  • likely by collaborating with CTCF, RBPJ may participate in establishing chromatin domains and/or long-range chromatin interactions that could be propagated through cell division to maintain gene expression programs
  • POU2F1 regulates IL17A expression by directing interchromosomal associations in conjunction with CTCF in T cells
  • interacts with the centromeric protein CENPE, CTCF helps recruit CENPE to the centromere during mitosis and it may do so through a structure stabilized by the CTCF/CENPE complex
  • SMARCA5 plays a major role organising arrays of nucleosomes adjacent to the binding sites for the architectural transcription factor CTCF sites and acts to promote CTCF binding
  • BRD2 is associated with the chromatin insulator CTCF and the cohesin complex to support cis-regulatory enhancer assembly for gene transcriptional activation
  • CTCF recruits BRD2 to co-bound sites whereas BRD2 is dispensable for CTCF occupancy, and BRD2 cooperates with CTCF to enforce transcriptional and architectural boundaries
  • both LDB1 and CTCF are required for enhancer-CA2 looping, and the domain of LDB1 contacted by CTCF is necessary to rescue CA2 transcription in LDB1-deficient cells
  • subtelomeric CTCF facilitates telomeric DNA replication by promoting DMRT2 transcription
  • CTCF is a novel regulator of TH transcription in the forebrain
  • STAG1 preferentially contributes to the stabilization of topologically associating domain boundaries together with CTCF, whereas STAG2 promotes cell-type-specific contacts between enhancers and promoters independently of CTCF
  • interaction between MAGEA1 and CTCF, which is required for the binding of MAGEA1 to the CTCFL promoter and is critical for the recruitment of DNMT3A
  • cell & other
    corresponding disease(s) MRD21
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in Wilms tumor(without LOI of H19)
    constitutional germinal mutation      
    de novo mutation in CTCF in individuals with intellectual disability, microcephaly, and growth retardation
    Susceptibility to asthma
    Variant & Polymorphism SNP increasing the risk of asthma
    Candidate gene
    Therapy target