CTCF is a major protein involved in insulator activity.

The protein CTCF plays heavily in the role of repressing the insulin-like growth factor 2 gene, by binding to the H-19 imprinting control region (ICR) along with Differentially-methylated Region-1 (DMR1) and MAR3.cite journal | author = Ohlsson R, Renkawitz R, Lobanenkov V | title = CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease | journal = Trends Genet. | volume = 17 | issue = 9 | pages = 520–7 | year = 2001 | pmid = 11525835 | doi = 10.1016/S0168-9525(01)02366-6 | issn = ] cite journal | author = Dunn KL, Davie JR | title = The many roles of the transcriptional regulator CTCF | journal = Biochem. Cell Biol. | volume = 81 | issue = 3 | pages = 161–7 | year = 2003 | pmid = 12897849 | doi = 10.1139/o03-052 | issn = ]

Binding of targeting sequence elements by CTCF can block the interaction between enhancers and promoters, therefore limiting the activity of enhancers to certain functional domains. Besides acting as enhancer blocking, CTCF can also act as a chromatin barrier by preventing the spread of heterochromatin structures.

In 2007, two independent studies (Xie et al. from MIT and Kim et al. from UCSD) revealed that the human genome contains nearly 15,000 CTCF insulator sites, suggesting a wide-spread role of CTCF in gene regulation.cite journal | author = Xie X, Mikkelsen TS, Gnirke A, Lindblad-Toh K, Kellis M, Lander ES | title = Systematic discovery of regulatory motifs in conserved regions of the human genome, including thousands of CTCF insulator sites | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 104 | issue = 17 | pages = 7145–50 | year = 2007 | pmid = 17442748 | doi = 10.1073/pnas.0701811104 | issn = ] cite journal | author = Kim TH, Abdullaev ZK, Smith AD, Ching KA, Loukinov DI, Green RD, Zhang MQ, Lobanenkov VV, Ren B | title = Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome | journal = Cell | volume = 128 | issue = 6 | pages = 1231–45 | year = 2007 | pmid = 17382889 | doi = 10.1016/j.cell.2006.12.048 | issn = ]


Further reading

citations =
*cite journal | author=Ohlsson R, Renkawitz R, Lobanenkov V |title=CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. |journal=Trends Genet. |volume=17 |issue= 9 |pages= 520–7 |year= 2001 |pmid= 11525835 |doi=
*cite journal | author=Klenova EM, Morse HC, Ohlsson R, Lobanenkov VV |title=The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer. |journal=Semin. Cancer Biol. |volume=12 |issue= 5 |pages= 399–414 |year= 2003 |pmid= 12191639 |doi=
*cite journal | author=Kuhn EJ, Geyer PK |title=Genomic insulators: connecting properties to mechanism. |journal=Curr. Opin. Cell Biol. |volume=15 |issue= 3 |pages= 259–65 |year= 2004 |pmid= 12787766 |doi=
*cite journal | author=Recillas-Targa F, De La Rosa-Velázquez IA, Soto-Reyes E, Benítez-Bribiesca L |title=Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection and its role in carcinogenesis. |journal=J. Cell. Mol. Med. |volume=10 |issue= 3 |pages= 554–68 |year= 2007 |pmid= 16989720 |doi=
*cite journal | author=Filippova GN, Fagerlie S, Klenova EM, "et al." |title=An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes. |journal=Mol. Cell. Biol. |volume=16 |issue= 6 |pages= 2802–13 |year= 1996 |pmid= 8649389 |doi=
*cite journal | author=Vostrov AA, Quitschke WW |title=The zinc finger protein CTCF binds to the APBbeta domain of the amyloid beta-protein precursor promoter. Evidence for a role in transcriptional activation. |journal=J. Biol. Chem. |volume=272 |issue= 52 |pages= 33353–9 |year= 1998 |pmid= 9407128 |doi=
*cite journal | author=Filippova GN, Lindblom A, Meincke LJ, "et al." |title=A widely expressed transcription factor with multiple DNA sequence specificity, CTCF, is localized at chromosome segment 16q22.1 within one of the smallest regions of overlap for common deletions in breast and prostate cancers. |journal=Genes Chromosomes Cancer |volume=22 |issue= 1 |pages= 26–36 |year= 1998 |pmid= 9591631 |doi=
*cite journal | author=Bell AC, West AG, Felsenfeld G |title=The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. |journal=Cell |volume=98 |issue= 3 |pages= 387–96 |year= 1999 |pmid= 10458613 |doi=
*cite journal | author=Pérez-Juste G, García-Silva S, Aranda A |title=An element in the region responsible for premature termination of transcription mediates repression of c-myc gene expression by thyroid hormone in neuroblastoma cells. |journal=J. Biol. Chem. |volume=275 |issue= 2 |pages= 1307–14 |year= 2000 |pmid= 10625678 |doi=
*cite journal | author=Lutz M, Burke LJ, Barreto G, "et al." |title=Transcriptional repression by the insulator protein CTCF involves histone deacetylases. |journal=Nucleic Acids Res. |volume=28 |issue= 8 |pages= 1707–13 |year= 2000 |pmid= 10734189 |doi=
*cite journal | author=Bell AC, Felsenfeld G |title=Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. |journal=Nature |volume=405 |issue= 6785 |pages= 482–5 |year= 2000 |pmid= 10839546 |doi= 10.1038/35013100
*cite journal | author=Hark AT, Schoenherr CJ, Katz DJ, "et al." |title=CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. |journal=Nature |volume=405 |issue= 6785 |pages= 486–9 |year= 2000 |pmid= 10839547 |doi= 10.1038/35013106
*cite journal | author=Chernukhin IV, Shamsuddin S, Robinson AF, "et al." |title=Physical and functional interaction between two pluripotent proteins, the Y-box DNA/RNA-binding factor, YB-1, and the multivalent zinc finger factor, CTCF. |journal=J. Biol. Chem. |volume=275 |issue= 38 |pages= 29915–21 |year= 2000 |pmid= 10906122 |doi= 10.1074/jbc.M001538200
*cite journal | author=Chao W, Huynh KD, Spencer RJ, "et al." |title=CTCF, a candidate trans-acting factor for X-inactivation choice. |journal=Science |volume=295 |issue= 5553 |pages= 345–7 |year= 2002 |pmid= 11743158 |doi= 10.1126/science.1065982
*cite journal | author=Dintilhac A, Bernués J |title=HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences. |journal=J. Biol. Chem. |volume=277 |issue= 9 |pages= 7021–8 |year= 2002 |pmid= 11748221 |doi= 10.1074/jbc.M108417200
*cite journal | author=Filippova GN, Qi CF, Ulmer JE, "et al." |title=Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity. |journal=Cancer Res. |volume=62 |issue= 1 |pages= 48–52 |year= 2002 |pmid= 11782357 |doi=
*cite journal | author=Jia L, Young MF, Powell J, "et al." |title=Gene expression profile of human bone marrow stromal cells: high-throughput expressed sequence tag sequencing analysis. |journal=Genomics |volume=79 |issue= 1 |pages= 7–17 |year= 2002 |pmid= 11827452 |doi= 10.1006/geno.2001.6683
*cite journal | author=Kanduri M, Kanduri C, Mariano P, "et al." |title=Multiple nucleosome positioning sites regulate the CTCF-mediated insulator function of the H19 imprinting control region. |journal=Mol. Cell. Biol. |volume=22 |issue= 10 |pages= 3339–44 |year= 2002 |pmid= 11971967 |doi=
*cite journal | author=Farrell CM, West AG, Felsenfeld G |title=Conserved CTCF insulator elements flank the mouse and human beta-globin loci. |journal=Mol. Cell. Biol. |volume=22 |issue= 11 |pages= 3820–31 |year= 2002 |pmid= 11997516 |doi=

External links


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