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Gene Review

CTCF  -  CCCTC-binding factor (zinc finger protein)

Gallus gallus

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Disease relevance of CTCF


High impact information on CTCF

  • This HS contains a binding site for the transcription factor CTCF [2].
  • The 5'-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix-associated element [3].
  • In this report we show that both CTCF and the HS4 insulator element are incorporated in the matrix; HS4 incorporation depends on the presence of an intact CTCF-binding site [3].
  • Purification of CTCF has revealed that it interacts with proteins involved in subnuclear architecture, notably nucleophosmin, a 38-kDa nucleolar phosphoprotein that is concentrated in nuclear matrix preparations [3].
  • We previously reported that a single CTCF-binding site in 5'HS4 is necessary and sufficient for enhancer blocking [4].

Biological context of CTCF

  • HS4 contains a binding site for CTCF that is necessary and sufficient for insulator action [3].
  • The protein CTCF plays an essential role in the action of a widely distributed class of vertebrate enhancer-blocking insulators, of which the first example was found in a DNA sequence element, HS4, at the 5' end of the chicken beta-globin locus [3].
  • A novel sequence-specific DNA-binding protein, CTCF, which interacts with the chicken c-myc gene promoter, has been identified and partially characterized (V. V. Lobanenkov, R. H. Nicolas, V. V. Adler, H. Paterson, E. M. Klenova, A. V. Polotskaja, and G. H. Goodwin, Oncogene 5:1743-1753, 1990) [5].
  • A CTCF-dependent silencer located in the differentially methylated area may regulate expression of a housekeeping gene overlapping a tissue-specific gene domain [6].
  • Here, we show that an 0.2-kb DNA fragment located approximately 4 kb upstream to the chicken alpha-globin gene cluster contains a binding site for the multifunctional protein factor CTCF and possesses silencer activity which depends on CTCF binding, as demonstrated by site-directed mutagenesis of the CTCF recognition sequence [6].

Anatomical context of CTCF

  • We detected six major nuclear forms of CTCF protein differentially expressed in different chicken cell lines and tissues [5].
  • The data are discussed in terms of the hypothesis that the CTCF-dependent silencer stabilizes the level of ggPRX gene transcription in erythroid cells where the promoter of this gene may be influenced by positive cis-regulatory signals activating alpha-globin gene transcription [6].
  • CTCF was found to be associated with this recognition site in erythroid cells but not in lymphoid cells where the site is methylated [6].
  • These results suggest that differential ICR methylation in the female and male germ lines is not acquired through differential binding of CTCF [7].

Associations of CTCF with chemical compounds

  • Mutation of the individual serines reveals that Serine 612 is a critical residue in regulation of CTCF by CK2 [8].

Physical interactions of CTCF

  • In addition, we showed that completely preventing phosphorylation by substituting all serines within this site resulted in markedly enhanced repression of the CTS-bearing vertebrate c-myc promoters, but did not alter CTCF nuclear localization or in vitro DNA-binding characteristics assayed with c-myc CTSs [9].


  1. Pax6 Regulation in Retinal Cells by CCCTC Binding Factor. Li, T., Lu, Z., Lu, L. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  2. Structural and functional conservation at the boundaries of the chicken beta-globin domain. Saitoh, N., Bell, A.C., Recillas-Targa, F., West, A.G., Simpson, M., Pikaart, M., Felsenfeld, G. EMBO J. (2000) [Pubmed]
  3. The 5'-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix-associated element. Yusufzai, T.M., Felsenfeld, G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Position-effect protection and enhancer blocking by the chicken beta-globin insulator are separable activities. Recillas-Targa, F., Pikaart, M.J., Burgess-Beusse, B., Bell, A.C., Litt, M.D., West, A.G., Gaszner, M., Felsenfeld, G. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. CTCF, a conserved nuclear factor required for optimal transcriptional activity of the chicken c-myc gene, is an 11-Zn-finger protein differentially expressed in multiple forms. Klenova, E.M., Nicolas, R.H., Paterson, H.F., Carne, A.F., Heath, C.M., Goodwin, G.H., Neiman, P.E., Lobanenkov, V.V. Mol. Cell. Biol. (1993) [Pubmed]
  6. A CTCF-dependent silencer located in the differentially methylated area may regulate expression of a housekeeping gene overlapping a tissue-specific gene domain. Klochkov, D., Rincón-Arano, H., Ioudinkova, E.S., Valadez-Graham, V., Gavrilov, A., Recillas-Targa, F., Razin, S.V. Mol. Cell. Biol. (2006) [Pubmed]
  7. The chicken beta-globin insulator element conveys chromatin boundary activity but not imprinting at the mouse Igf2/H19 domain. Szabó, P.E., Tang, S.H., Reed, M.R., Silva, F.J., Tsark, W.M., Mann, J.R. Development (2002) [Pubmed]
  8. Regulation of the transcription factor, CTCF, by phosphorylation with protein kinase CK2. El-Kady, A., Klenova, E. FEBS Lett. (2005) [Pubmed]
  9. Functional phosphorylation sites in the C-terminal region of the multivalent multifunctional transcriptional factor CTCF. Klenova, E.M., Chernukhin, I.V., El-Kady, A., Lee, R.E., Pugacheva, E.M., Loukinov, D.I., Goodwin, G.H., Delgado, D., Filippova, G.N., León, J., Morse, H.C., Neiman, P.E., Lobanenkov, V.V. Mol. Cell. Biol. (2001) [Pubmed]
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