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CCCTC-binding factor (zinc finger protein)

PDB rendering based on 1x6h.
Available structures
1x6h, 2ct1
Identifiers
Symbols CTCF;
External IDs OMIM604167 MGI109447 HomoloGene4786 GeneCards: CTCF Gene
RNA expression pattern
PBB GE CTCF 202521 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 10664 13018
Ensembl ENSG00000102974 ENSMUSG00000005698
UniProt P49711 Q05CK6
RefSeq (mRNA) NM_006565 NM_007794
RefSeq (protein) NP_006556 NP_031820
Location (UCSC) Chr 16:
66.15 - 66.23 Mb
Chr 8:
108.53 - 108.57 Mb
PubMed search [1] [2]

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.[1][2]

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 widespread role of CTCF in gene regulation.[3][4]

In 2008, It was further revealed that CTCF binding sites act as nucleosome positioning anchors so that, when used to align various genomic signals, multiple flanking nucleosomes can be readily identified.[5]

Contents

Interactions

CTCF has been shown to interact with Y box binding protein 1.[6]

References

  1. ^ Ohlsson R, Renkawitz R, Lobanenkov V (2001). "CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease". Trends Genet. 17 (9): 520–7. doi:10.1016/S0168-9525(01)02366-6. PMID 11525835.  
  2. ^ Dunn KL, Davie JR (2003). "The many roles of the transcriptional regulator CTCF". Biochem. Cell Biol. 81 (3): 161–7. doi:10.1139/o03-052. PMID 12897849.  
  3. ^ Xie X, Mikkelsen TS, Gnirke A, Lindblad-Toh K, Kellis M, Lander ES (2007). "Systematic discovery of regulatory motifs in conserved regions of the human genome, including thousands of CTCF insulator sites". Proc. Natl. Acad. Sci. U.S.A. 104 (17): 7145–50. doi:10.1073/pnas.0701811104. PMID 17442748.  
  4. ^ Kim TH, Abdullaev ZK, Smith AD, Ching KA, Loukinov DI, Green RD, Zhang MQ, Lobanenkov VV, Ren B (2007). "Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome". Cell 128 (6): 1231–45. doi:10.1016/j.cell.2006.12.048. PMID 17382889.  
  5. ^ Fu Y, Sinha M, Peterson CL, Weng Z (2008). "The insulator binding protein CTCF positions 20 nucleosomes around its binding sites across the human genome". PLoS genetics 4 (7): e1000138. doi:10.1371/journal.pgen.1000138. PMID 18654629.  
  6. ^ Chernukhin, I V; Shamsuddin S, Robinson A F, Carne A F, Paul A, El-Kady A I, Lobanenkov V V, Klenova E M (Sep. 2000). "Physical and functional interaction between two pluripotent proteins, the Y-box DNA/RNA-binding factor, YB-1, and the multivalent zinc finger factor, CTCF". J. Biol. Chem. (UNITED STATES) 275 (38): 29915–21. doi:10.1074/jbc.M001538200. ISSN 0021-9258. PMID 10906122.  

Further reading

  • Ohlsson R, Renkawitz R, Lobanenkov V (2001). "CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease.". Trends Genet. 17 (9): 520–7. doi:10.1016/S0168-9525(01)02366-6. PMID 11525835.  
  • Klenova EM, Morse HC, Ohlsson R, Lobanenkov VV (2003). "The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer.". Semin. Cancer Biol. 12 (5): 399–414. doi:10.1016/S1044-579X(02)00060-3. PMID 12191639.  
  • Kuhn EJ, Geyer PK (2004). "Genomic insulators: connecting properties to mechanism.". Curr. Opin. Cell Biol. 15 (3): 259–65. doi:10.1016/S0955-0674(03)00039-5. PMID 12787766.  
  • Recillas-Targa F, De La Rosa-Velázquez IA, Soto-Reyes E, Benítez-Bribiesca L (2007). "Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection and its role in carcinogenesis.". J. Cell. Mol. Med. 10 (3): 554–68. doi:10.1111/j.1582-4934.2006.tb00420.x. PMID 16989720.  
  • Filippova GN, Fagerlie S, Klenova EM, et al. (1996). "An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes.". Mol. Cell. Biol. 16 (6): 2802–13. PMID 8649389.  
  • Vostrov AA, Quitschke WW (1998). "The zinc finger protein CTCF binds to the APBbeta domain of the amyloid beta-protein precursor promoter. Evidence for a role in transcriptional activation.". J. Biol. Chem. 272 (52): 33353–9. doi:10.1074/jbc.272.52.33353. PMID 9407128.  
  • Filippova GN, Lindblom A, Meincke LJ, et al. (1998). "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.". Genes Chromosomes Cancer 22 (1): 26–36. doi:10.1002/(SICI)1098-2264(199805)22:1<26::AID-GCC4>3.0.CO;2-9. PMID 9591631.  
  • Bell AC, West AG, Felsenfeld G (1999). "The protein CTCF is required for the enhancer blocking activity of vertebrate insulators.". Cell 98 (3): 387–96. doi:10.1016/S0092-8674(00)81967-4. PMID 10458613.  
  • Pérez-Juste G, García-Silva S, Aranda A (2000). "An element in the region responsible for premature termination of transcription mediates repression of c-myc gene expression by thyroid hormone in neuroblastoma cells.". J. Biol. Chem. 275 (2): 1307–14. doi:10.1074/jbc.275.2.1307. PMID 10625678.  
  • Lutz M, Burke LJ, Barreto G, et al. (2000). "Transcriptional repression by the insulator protein CTCF involves histone deacetylases.". Nucleic Acids Res. 28 (8): 1707–13. doi:10.1093/nar/28.8.1707. PMID 10734189.  
  • Bell AC, Felsenfeld G (2000). "Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene.". Nature 405 (6785): 482–5. doi:10.1038/35013100. PMID 10839546.  
  • Hark AT, Schoenherr CJ, Katz DJ, et al. (2000). "CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus.". Nature 405 (6785): 486–9. doi:10.1038/35013106. PMID 10839547.  
  • Chernukhin IV, Shamsuddin S, Robinson AF, et al. (2000). "Physical and functional interaction between two pluripotent proteins, the Y-box DNA/RNA-binding factor, YB-1, and the multivalent zinc finger factor, CTCF.". J. Biol. Chem. 275 (38): 29915–21. doi:10.1074/jbc.M001538200. PMID 10906122.  
  • Chao W, Huynh KD, Spencer RJ, et al. (2002). "CTCF, a candidate trans-acting factor for X-inactivation choice.". Science 295 (5553): 345–7. doi:10.1126/science.1065982. PMID 11743158.  
  • Dintilhac A, Bernués J (2002). "HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences.". J. Biol. Chem. 277 (9): 7021–8. doi:10.1074/jbc.M108417200. PMID 11748221.  
  • Filippova GN, Qi CF, Ulmer JE, et al. (2002). "Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity.". Cancer Res. 62 (1): 48–52. PMID 11782357.  
  • Jia L, Young MF, Powell J, et al. (2002). "Gene expression profile of human bone marrow stromal cells: high-throughput expressed sequence tag sequencing analysis.". Genomics 79 (1): 7–17. doi:10.1006/geno.2001.6683. PMID 11827452.  
  • Kanduri M, Kanduri C, Mariano P, et al. (2002). "Multiple nucleosome positioning sites regulate the CTCF-mediated insulator function of the H19 imprinting control region.". Mol. Cell. Biol. 22 (10): 3339–44. doi:10.1128/MCB.22.10.3339-3344.2002. PMID 11971967.  
  • Farrell CM, West AG, Felsenfeld G (2002). "Conserved CTCF insulator elements flank the mouse and human beta-globin loci.". Mol. Cell. Biol. 22 (11): 3820–31. doi:10.1128/MCB.22.11.3820-3831.2002. PMID 11997516.  

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