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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Gene Review: 

Ctcf  -  CCCTC-binding factor

Mus musculus

Synonyms: 11-zinc finger protein, AW108038, CTCFL paralog, Transcriptional repressor CTCF
 
 
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Disease relevance of Ctcf

  • A chromatin insulator-like element in the herpes simplex virus type 1 latency-associated transcript region binds CCCTC-binding factor and displays enhancer-blocking and silencing activities [1].
 

High impact information on Ctcf

  • Four repeats in the DMD bind CCCTC-binding factor (CTCF) on the maternal allele and have been proposed to attract methylation on the paternal allele [2].
  • To test whether DNA insulators can act as boundaries on the X chromosome, we inserted into the mouse X-linked Hprt locus a GFP transgene flanked with zero, one, or two copies of a prototypic vertebrate insulator from the chicken beta-globin locus, chicken hypersensitive site 4, which contains CCCTC binding factor binding sites [3].
  • The flanking HSs bind CCCTC binding factor (CTCF) and are thought to interact with the LCR to form a "chromatin hub" involved in beta-globin gene activation [4].
  • We have previously shown that maternal inheritance of mutated (three of the four) target sites for the 11-zinc finger protein CTCF leads to loss of Igf2 imprinting [5].
  • All known vertebrate chromatin insulators interact with the highly conserved, multivalent 11-zinc finger nuclear factor CTCF to demarcate expression domains by blocking enhancer or silencer signals in a position-dependent manner [6].
 

Biological context of Ctcf

  • In somatic cells, the maternally and paternally derived ICRs are hypo- and hypermethylated, respectively, with the former binding the insulator protein CCCTC-binding factor (CTCF) and acting to block access of enhancers to the Igf2 promoter [7].

References

  1. A chromatin insulator-like element in the herpes simplex virus type 1 latency-associated transcript region binds CCCTC-binding factor and displays enhancer-blocking and silencing activities. Amelio, A.L., McAnany, P.K., Bloom, D.C. J. Virol. (2006) [Pubmed]
  2. Antagonism between DNA hypermethylation and enhancer-blocking activity at the H19 DMD is uncovered by CpG mutations. Engel, N., West, A.G., Felsenfeld, G., Bartolomei, M.S. Nat. Genet. (2004) [Pubmed]
  3. A DNA insulator prevents repression of a targeted X-linked transgene but not its random or imprinted X inactivation. Ciavatta, D., Kalantry, S., Magnuson, T., Smithies, O. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Flanking HS-62.5 and 3' HS1, and regions upstream of the LCR, are not required for beta-globin transcription. Bender, M.A., Byron, R., Ragoczy, T., Telling, A., Bulger, M., Groudine, M. Blood (2006) [Pubmed]
  5. Mutation of a single CTCF target site within the H19 imprinting control region leads to loss of Igf2 imprinting and complex patterns of de novo methylation upon maternal inheritance. Pant, V., Kurukuti, S., Pugacheva, E., Shamsuddin, S., Mariano, P., Renkawitz, R., Klenova, E., Lobanenkov, V., Ohlsson, R. Mol. Cell. Biol. (2004) [Pubmed]
  6. The binding sites for the chromatin insulator protein CTCF map to DNA methylation-free domains genome-wide. Mukhopadhyay, R., Yu, W., Whitehead, J., Xu, J., Lezcano, M., Pack, S., Kanduri, C., Kanduri, M., Ginjala, V., Vostrov, A., Quitschke, W., Chernukhin, I., Klenova, E., Lobanenkov, V., Ohlsson, R. Genome Res. (2004) [Pubmed]
  7. Parent-of-origin-specific binding of nuclear hormone receptor complexes in the H19-Igf2 imprinting control region. Szabó, P.E., Pfeifer, G.P., Mann, J.R. Mol. Cell. Biol. (2004) [Pubmed]
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