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Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;10(3):554–568. doi: 10.1111/j.1582-4934.2006.tb00420.x

Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection and its role in carcinogenesis

Felix Recillas-Targa a,*, Inti A De La Rosa-Velázquez a, Ernesto Soto-Reyes a, Luis Benítez-Bribiesca b
PMCID: PMC3933142  PMID: 16989720

Abstract

Genetic and epigenetic regulations are essential mechanisms that ensure proper early and subsequent mammalian programming of diverse cellular processes. These mechanisms affect transcriptional regulation, stem cell determination and cell cycle control, including senescence and aging. It is not surprising that perturbation of the exquisite balance between genetic and epigenetic regulation can lead to diverse diseases, including cancer. Histone covalent modifications and DNA methylation do not explain all epigenetic phenomena. We describe a previously unsuspected epigenetic factor and propose the incorporation of the 11-zinc finger CCCTC-binding factor, known as CTCF as a novel and multifunctional epigenetic regulator.

Keywords: epigenetic, CTCF and BORIS nuclear factors, intergenic transcripts, chromatin, DNA methylation, histone modification, insulator, carcinogenesis, tumour suppressor gene

References

  • 1.Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004;429:457–63. doi: 10.1038/nature02625. [DOI] [PubMed] [Google Scholar]
  • 2.Lund AH, van Lohuizen M. Epigenetics and cancer. Genes Dev. 2004;18:2315–35. doi: 10.1101/gad.1232504. [DOI] [PubMed] [Google Scholar]
  • 3.Esteller M. Epigenetics provides a new generation of oncogenes and tumour-suppressor genes. Br J Cancer. 2006;94:179–83. doi: 10.1038/sj.bjc.6602918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;10:6–21. doi: 10.1101/gad.947102. [DOI] [PubMed] [Google Scholar]
  • 5.Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates instrinsic and environmental signals. Nat. Genet. 2003;33:245–54. doi: 10.1038/ng1089. [DOI] [PubMed] [Google Scholar]
  • 6.Narita M, Nunez S, Heard E, Narita M, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell. 2003;113:703–16. doi: 10.1016/s0092-8674(03)00401-x. [DOI] [PubMed] [Google Scholar]
  • 7.Santos F, Zakhartchenko V, Stojkovic M, Peters A, Jenuwein T, Wolf E, Reik W, Dean W. Epigenetic marking correlates with development potential in cloned bovine preimplantation embryos. Curr Biol. 2003;13:1116–21. doi: 10.1016/s0960-9822(03)00419-6. [DOI] [PubMed] [Google Scholar]
  • 8.Gonzalo S, Garcia-Cao M, Fraga MF, Schotta G, Peters AH, Cotter SE, Eguia R, Dean DC, Esteller M, Jenuwein T, Blasco MA. Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat Cell Biol. 2005;7:420–8. doi: 10.1038/ncb1235. [DOI] [PubMed] [Google Scholar]
  • 9.Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Annu Rev Biochem. 2005;74:481–514. doi: 10.1146/annurev.biochem.74.010904.153721. [DOI] [PubMed] [Google Scholar]
  • 10.Wolffe AP, Matzke MA. Epigenetics: regulation through repression. Science. 1999;286:481–6. doi: 10.1126/science.286.5439.481. [DOI] [PubMed] [Google Scholar]
  • 11.Li E. Chromatin modifications and epigenetic reprogramming in mammalian development. Nat Rev Genet. 2002;3:662–73. doi: 10.1038/nrg887. [DOI] [PubMed] [Google Scholar]
  • 12.Esteller M. Dormant hypermethylated tumour suppressor genes: questions and answers. J Pathol. 2005;205:172–80. doi: 10.1002/path.1707. [DOI] [PubMed] [Google Scholar]
  • 13.Recillas-Targa F. DNA methylation, chromatin boundaries and mechanisms of genomic imprinting. Arch Med Res. 2002;33:428–38. doi: 10.1016/s0188-4409(02)00366-1. [DOI] [PubMed] [Google Scholar]
  • 14.Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003;349:2042–54. doi: 10.1056/NEJMra023075. [DOI] [PubMed] [Google Scholar]
  • 15.Antequera F. Structure, function and evolution of CpG island promoters. Cell Mol Life Sci. 2003;60:1647–58. doi: 10.1007/s00018-003-3088-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Grady WM, Willis J, Guilford PJ, Dundier AK, Toro TT, Lynch H, Wiesner G, Ferguson K, Eng C, Park JG, Kim SJ, Markowitz S. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet. 2000;26:16–7. doi: 10.1038/79120. [DOI] [PubMed] [Google Scholar]
  • 17.Chen W, Cooper TK, Zahnow CA, Overhltser M, Zhao Z, Ladanyi M, Karp JE, Gokgoz N, Wunder JS, Andrulis IL, Levine AJ, Mankowski JB, Baylin SB. Epigenetic and genetic loss of Hic function accentuates the role of p53 in tumorigenesis. Cancer Cell. 2004;6:387–98. doi: 10.1016/j.ccr.2004.08.030. [DOI] [PubMed] [Google Scholar]
  • 18.Baylin SB, Ohm JE. Epigenetic gene silencing in cancer-a mechanism for early oncogenic pathway addiction. Nat Rev Cancer. 2006;6:107–16. doi: 10.1038/nrc1799. [DOI] [PubMed] [Google Scholar]
  • 19.Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983;301:89–92. doi: 10.1038/301089a0. [DOI] [PubMed] [Google Scholar]
  • 20.Goelz SE, Vogelstein B, Hamilton SR, Feinberg AP. Hypomethylation of DNA from benign and malignant human colon neoplasms. Science. 1985;228:187–90. doi: 10.1126/science.2579435. [DOI] [PubMed] [Google Scholar]
  • 21.Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet. 2006;7:21–33. doi: 10.1038/nrg1748. [DOI] [PubMed] [Google Scholar]
  • 22.Tilghman SM. The sins of the fathers and mothers: genomic imprinting in mammalian development. Cell. 1999;96:185–93. doi: 10.1016/s0092-8674(00)80559-0. [DOI] [PubMed] [Google Scholar]
  • 23.Reik W, Murrell A, Lewis A, Mitsuya K, Umlauf D, Dean W, Higgins M, Feil R. Chromosome loops, insulators and histone methylation: new insights into regulation of imprinting in clusters. Cold Spring Harbor Symposia on Quantitative Biology. 2004;LXIX:29–37. doi: 10.1101/sqb.2004.69.29. [DOI] [PubMed] [Google Scholar]
  • 24.Issa J-P. CpG island methylator phenotype in cancer. Nat Rev Cancer. 2004;4:988–93. doi: 10.1038/nrc1507. [DOI] [PubMed] [Google Scholar]
  • 25.Hake SB, Xiao A, Allis CD. Linking the epigenetic “language” of covalent histone modifications to cancer. Br J Cancer. 2004;90:761–9. doi: 10.1038/sj.bjc.6601575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Orphanides G, Reinberg D. A unified theory of gene expression. Cell. 2002;108:439–51. doi: 10.1016/s0092-8674(02)00655-4. [DOI] [PubMed] [Google Scholar]
  • 27.Hahn S. Structure and mechanism of the RNA polymerase II transcription machinery. Nat Struct Mol Biol. 2004;11:394–403. doi: 10.1038/nsmb763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Ohlsson R, Renkawitz R, Lobanenkov VV. CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. Trends Genet. 2001;17:520–7. doi: 10.1016/s0168-9525(01)02366-6. [DOI] [PubMed] [Google Scholar]
  • 29.Klenova E, Ohlsson R. Poly(ADP-ribosyl)ation and epigenetics. Is CTCF part of the plot. Cell Cycle. 2005;4:96–101. doi: 10.4161/cc.4.1.1398. [DOI] [PubMed] [Google Scholar]
  • 30.El-Kady A, Klenova E. Regulation of the transcription factor, CTCF by phosphorylation with protein kinase CK2. FEBS Lett. 2005;579:1424–34. doi: 10.1016/j.febslet.2005.01.044. [DOI] [PubMed] [Google Scholar]
  • 31.Yu W, Ginjala V, Pant V, Chernukhin I, Whitehead J, Docquier F, Farrar D, Tavoosidana G, Mukhopadhyay R, Kanduri C, Oshimura M, Feinberg AP, Lobanenkov V, Klenova E, Ohlsson R. Poly(ADP-ribosyl)ation regulated CTCF-dependent chromatin insulation. Nat Genet. 2004;36:1105–1110. doi: 10.1038/ng1426. [DOI] [PubMed] [Google Scholar]
  • 32.Vatolin S, Abdullaev Z, Pack SD, Flanagan PT, Custer M, Loukinov DI, Pugacheva E, Hong JA, Morse H, 3rd, Schrump DS, Risinger JI, Barrett JC, Lobanenkov VV. Conditional expression of the CTCF-paralogous transcriptional factor BORIS in normal cells results in demethylation and derepression of MAGE-A1 and reactivation of other cancer-testis genes. Cancer Res. 2005;65:7751–62. doi: 10.1158/0008-5472.CAN-05-0858. [DOI] [PubMed] [Google Scholar]
  • 33.Hong JA, Kang Y, Abdullaev Z, Flanagan PT, Pack SD, Fischette MR. Reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter coincides with derepression of this cancer-testis gene in lung cancer cells. Cancer Res. 2005;65:7763–74. doi: 10.1158/0008-5472.CAN-05-0823. [DOI] [PubMed] [Google Scholar]
  • 34.Lewis A, Murrell A. Genomic imprinting: CTCF protects the boundaries. Curr Biol. 2004;14:R284–6. doi: 10.1016/j.cub.2004.03.026. [DOI] [PubMed] [Google Scholar]
  • 35.Yoon B, Herman H, Hu B, Park YJ, Lindroth A, Bell A, West AG, Chang Y, Stablewski A, Piel JC, Loukinov DI, Lobanenkov VV, Soloway PD. Rasgrfl imprinting is regulated by a CTCF-dependent methylation-sensitive enhancer blocker. Mol Cell Biol. 2005;25:11184–90. doi: 10.1128/MCB.25.24.11184-11190.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Rosa AL, Wu YQ, Kwabi-Addo B, Coveler KJ, Reid Sutton V, Shaffer LG. Allele-specific methylation of a functional CTCF binding site upstream of MEG3 in the human imprinted domain of 14q32. Chromosome Res. 2005;13:809–18. doi: 10.1007/s10577-005-1015-4. [DOI] [PubMed] [Google Scholar]
  • 37.Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature. 2000;405:486–9. doi: 10.1038/35013106. [DOI] [PubMed] [Google Scholar]
  • 38.Bell AC, Felsenfeld G. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature. 2000;405:482–5. doi: 10.1038/35013100. [DOI] [PubMed] [Google Scholar]
  • 39.Fedoriw AM, Stein P, Svoboda P, Schultz RM, Bartolomei MS. Transgenic RNAi reveals essential function for CTCF in H19 gene imprinting. Science. 2004;303:238–40. doi: 10.1126/science.1090934. [DOI] [PubMed] [Google Scholar]
  • 40.Klenova EM, Morse HC, 3rd, Ohlsson R, Lobanenkov VV. The novel BORIS+CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer. Semin Cancer Biol. 2002;12:399–414. doi: 10.1016/s1044-579x(02)00060-3. [DOI] [PubMed] [Google Scholar]
  • 41.Loukinov DI, Pugacheva E, Vatolin S, Pack SD, Moon H, Chernukhin I, Mannan P, Larsson E, Kanduri C, Vostrov AA, Cui H, Niemitz EL, Rasko JE, Docquier FM, Kistler M, Breen JJ, Zhuang Z, Quitschke WW, Renkawitz R, Klenova EM, Feinberg AP, Ohlsson R, Morse HC, 3rd, Lobanenkov VV. BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma. Proc Natl Acad Sci USA. 2002;99:6806–11. doi: 10.1073/pnas.092123699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol. 2003;13:1192–220. doi: 10.1016/s0960-9822(03)00432-9. [DOI] [PubMed] [Google Scholar]
  • 43.Vire E, Brenner C, Deplus R, Blanchon L, Frga M, Didelot C, Morey L, van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, DiCroce L, DeLamoit Y, Fuks F. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2005;38:566–9. doi: 10.1038/nature04431. [DOI] [PubMed] [Google Scholar]
  • 44.Brown CJ, Greally JM. A stain upon the silence: genes escaping X inactivation. Trends Genet. 2003;19:432–8. doi: 10.1016/S0168-9525(03)00177-X. [DOI] [PubMed] [Google Scholar]
  • 45.Filippova GN, Cheng MK, Moore JM, Truong J-P, Hu YJ, Nguyen DK, Tsuchiya KD, Disteche CM. Boundaries between chromosomal domains of X inactivation and escape bind CTCF and lack CpG methylation during early development. Develop Cell. 2005;8:31–42. doi: 10.1016/j.devcel.2004.10.018. [DOI] [PubMed] [Google Scholar]
  • 46.Sado T, Okano M, Li E, Sasaki H. De novo DNA methylation is dispensable for the initiation and propagation of X chromosome inactivation. Development. 2004;131:975–82. doi: 10.1242/dev.00995. [DOI] [PubMed] [Google Scholar]
  • 47.Heard E. Delving into the diversity of facultative heterochromatin: the epigenetics of the inactive X chromosome. Curr Opin Genet Develop. 2005;15:482–9. doi: 10.1016/j.gde.2005.08.009. [DOI] [PubMed] [Google Scholar]
  • 48.Machuca-Tzili L, Brook D, Hilton-Jones D. Clinical and molecular aspects of the myotonic dystrophies. Muscle Nerve. 2005;32:1–18. doi: 10.1002/mus.20301. [DOI] [PubMed] [Google Scholar]
  • 49.Gatchel JR, Zoghbi HY. Diseases of unstable repeat expansion: mechanisms and common principles. Nat Rev Genet. 2005;6:743–55. doi: 10.1038/nrg1691. [DOI] [PubMed] [Google Scholar]
  • 50.Filippova GN, Thienes CP, Penn BH, Cho DH, Hu YJ, Moore JM, Klesert TR, Lobanenkov VV, Tapscott SJ. CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus. Nat Genet. 2001;28:335–43. doi: 10.1038/ng570. [DOI] [PubMed] [Google Scholar]
  • 51.Otten AD, Tapscott SJ. Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure. Proc Natl Acad Sci USA. 1995;92:5465–9. doi: 10.1073/pnas.92.12.5465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Cho DH, Thienes CP, Mahoney SE, Analau E, Filippova GN, Tapscott SJ. Antisense transcription and heterochromatin at the DM1 CTG repeats are constrained by CTCF. Mol Cell. 2005;20:483–9. doi: 10.1016/j.molcel.2005.09.002. [DOI] [PubMed] [Google Scholar]
  • 53.West AG, Gaszner M, Felsenfeld G. Insulators: many functions, many mechanisms. Genes Dev. 2002;16:271–88. doi: 10.1101/gad.954702. [DOI] [PubMed] [Google Scholar]
  • 54.Recillas-Targa F, Pikaart MJ, Burgess-Beusse B, Bell AC, Litt MD, West AG, Gaszner M, Felsenfeld G. Position-effect protection and enhancer blocking by the chicken β-globin insulator are separable activities. Proc Natl Acad Sci USA. 2002;99:6883–8. doi: 10.1073/pnas.102179399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Pikaart MJ, Recillas-Targa F, Felsenfeld G. Loss of transcriptional activity of a transgene is accompanied by DNA methylation and histone deacetylation and is prevented by insulators. Genes Dev. 1998;12:2852–62. doi: 10.1101/gad.12.18.2852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Lutz M, Burke LJ, LeFevre P, Myers FA, Thorne AW, Crane-Robinson C, Bonifer C, Filippova GN, Lobanenkov V, Renkawitz R. Thyroid hormone-regulated enhancer blocking: cooperation of CTCF and thyroid hormone receptor. EMBO J. 2003;22:1579–87. doi: 10.1093/emboj/cdg147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Farrell CM, West AG, Felsenfeld G. Conserved CTCF insulator elements flank the mouse and human β-globin loci. Mol Cell Biol. 2002;22:3820–31. doi: 10.1128/MCB.22.11.3820-3831.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Valadez-Graham V, Razin SV, Recillas-Targa F. CTCF-dependent enhancer blockers at the upstream region of the chicken α-globin gene domain. Nucleic Acids Res. 2004;32:1354–62. doi: 10.1093/nar/gkh301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Klochkov D, Rincón-Arano H, Ioudinnkowa ES, Valadez-Graham V, Gavrilov A, Recillas-Targa F, Razin SV. A CTCF-dependent silencer located in the differentially methylates area may regulate expression of a housekeeping gene overlapping a tissue-specific gene domain. Mol Cell Biol. 2006;26:1589–97. doi: 10.1128/MCB.26.5.1589-1597.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Burgess-Beusse B, Farrell C, Gaszner M, Litt M, Mutskov V, Recillas-Targa F, Simpson M, West A, Felsenfeld G. The insulation of genes from external enhancers and silencing chromatin. Proc Natl Acad Sci USA. 2002;99:16433–7. doi: 10.1073/pnas.162342499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Yusufzai TM, Tagami H, Nakatani Y, Felsenfeld G. CTCF tethers and insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol Cell. 2004;13:291–8. doi: 10.1016/s1097-2765(04)00029-2. [DOI] [PubMed] [Google Scholar]
  • 62.Bulger M, Schübeler D, Bender MA, Hamilton J, Farrell CM, Hardison RC, Groudine M. A complex chromatin landscape revealed by patterns of nuclease sensitivity and histone modification within the mouse β-globin locus. Mol Cell Biol. 2003;23:5234–44. doi: 10.1128/MCB.23.15.5234-5244.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Tolhuis B, Palstra RJ, Splinter E, Grosveld F, DeLaat W. Looping and interaction between hypersensitive sites in the active β-globin locus. Mol Cell. 2002;10:1453–65. doi: 10.1016/s1097-2765(02)00781-5. [DOI] [PubMed] [Google Scholar]
  • 64.Chakalova L, Debrand E, Mitchell JA, Osborne CS, Fraser P. Replication and transcription: shaping the landscape of the genome. Nat Rev Genet. 2005;6:669–77. doi: 10.1038/nrg1673. [DOI] [PubMed] [Google Scholar]
  • 65.Paltra R-J, Tolhuis B, Splinter E, Nijmeijer R, Grosveld F. DeLaat W. The β-globin nuclear compartment in development and erythroid differentiation. Nat Genet. 2003;35:190–4. doi: 10.1038/ng1244. [DOI] [PubMed] [Google Scholar]
  • 66.Gerasimova TI, Byrd K. Corces V. A chromatin insulator determines the nuclear localization of DNA. Mol Cell. 2000;6:1025–35. doi: 10.1016/s1097-2765(00)00101-5. [DOI] [PubMed] [Google Scholar]
  • 67.Capelson M, Corces VG. Boundary elements and nuclear organization. Biol Cell. 2004;96:617–29. doi: 10.1016/j.biolcel.2004.06.004. [DOI] [PubMed] [Google Scholar]
  • 68.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. The binding site for the chromatin insulator protein CTCF map to DNA methylation-free domains genome-wide. Genome Res. 2004;14:1594–602. doi: 10.1101/gr.2408304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Dunn KL, Zhao H, Devie JR. The insulator binding protein CTCF associated with the nuclear matrix. Exp Cell Res. 2003;288:218–23. doi: 10.1016/s0014-4827(03)00185-x. [DOI] [PubMed] [Google Scholar]
  • 70.Yusufzai TM, Felsenfeld G. The 5’-HS4 chicken β-globin insulator is a CTCF-dependent nuclear matrix-associated element. Proc Natl Acad Sci USA. 2004;101:8620–4. doi: 10.1073/pnas.0402938101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Murrell A, Heeson S, Reik W. Interaction between differentially methylated regions partitions the imprinted genes Igf2 and H19 into parent-specific chromatin loops. Nat Genet. 2004;36:889–93. doi: 10.1038/ng1402. [DOI] [PubMed] [Google Scholar]
  • 72.Spilianakis CG, Laliotis MD, Twon T, Lee GR, Flavell RA. Interchromosomal associations between alternatively expressed loci. Nature. 2005;435:637–45. doi: 10.1038/nature03574. [DOI] [PubMed] [Google Scholar]
  • 73.Ling JQ, Li T, Hu JF, Vu TH, Chen HL, Qui XW, Cherry AM, Hoffman AR. CTCF mediates interchromosomal colocalization between Igf2/H19 and. Wsb1/Nf1. Science. 2006;312:269–72. doi: 10.1126/science.1123191. [DOI] [PubMed] [Google Scholar]
  • 74.Cremer T, Cremer C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet. 2001;2:292–301. doi: 10.1038/35066075. [DOI] [PubMed] [Google Scholar]
  • 75.Rasko JE, Klenova EM, Leon J, Filippova GN, Loukinov DI, Vatolin S, Robinson AF, Hu YJ, Ulmer J, Ward MD, Pugacheva EM, Neiman PE, Morse HC, 3rd, Collins SJ, Lobanenkov VV. Cell growth inhibition by the multifunctional multivalent zinc-finger factor CTCF. Cancer Res. 2001;61:6002–7. [PubMed] [Google Scholar]
  • 76.Torrano V, Chernukhin I, Docquier F, D’Arcy V, Leon J, Klenova E, Delgado MD. CTCF regulates growth and erythroid differentiation of human myeloid leukemia cells. J Biol Chem. 2005;280:28152–61. doi: 10.1074/jbc.M501481200. [DOI] [PubMed] [Google Scholar]
  • 77.Docquier F, Farrar D, D’Arcy V, Chernukhin I, Robinson AF, Loukinov D, Vatolin S, Pack S, Mackay A, Harris RAN, Dorricott H, O’Hare MJ, Lobanenkov V, Klenova E. Heightened expression of CTCF in breast cancer cells is associated with resistance to apoptosis. Cancer Res. 2005;65:5112–22. doi: 10.1158/0008-5472.CAN-03-3498. [DOI] [PubMed] [Google Scholar]
  • 78.Filippova GN, Lindblom A, Meincke LJ, Klenova EM, Neiman PE, Collisn SJ, Doggett NA, Lobanenkov V. 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. 1998;22:26–36. [PubMed] [Google Scholar]
  • 79.Yeh A, Wei M, Golub SB, Yamashiro DJ, Murty VV, Tycko B. Chromosome arm 16q in Wilms tumors: unbalanced chromosomal translocations, loss of heterozygosity, and assessment of the CTCF gene. Genes Chromosomes Cancer. 2002;35:156–63. doi: 10.1002/gcc.10110. [DOI] [PubMed] [Google Scholar]
  • 80.Cui H, Niemitz EL, Ravenel JD, Onyango P, Brandenburg SA, Lobanenkov VV, Feinberg AP. Loss of imprinting of insulin-like growth factor-II in Wilm’s tumor commonly involves altered methylation but not mutations of CTCF or its binding site. Cancer Res. 2001;61:4947–50. [PubMed] [Google Scholar]
  • 81.Aulmann S, Bläker H, Penzel R, Rieker RJ, Otto HF, Sinn HP. CTCF gene mutations in invasive ductal breast cancer. Breast Cancer Res. 2003;80:347–52. doi: 10.1023/A:1024930404629. [DOI] [PubMed] [Google Scholar]
  • 82.Zhou X-L, Werelius B, Lindblom A. A screen for germ line mutations in the gene encoding CCCTC-binding factor (CTCF) in familial non-BRCA1/BRCA2 breast cancer. Breast Cancer Res. 2004;6:R187–90. doi: 10.1186/bcr774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83.Rakha EA, Pinder SE, Paish CE, Ellis IO. Expression of the transcription factor CTCF in invasive breast cancer: a candidate gene located at 16q22.1. Br J Cancer. 2004;91:1591–6. doi: 10.1038/sj.bjc.6602144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Butcher DT, Mancini-DiNarfo DN, Archer TK, Rodenhiser DI. DNA binding sites for putative methylation boundaries in the unmethylated region of the BRCA1 promoter. Int J Cancer. 2004;111:669–78. doi: 10.1002/ijc.20324. [DOI] [PubMed] [Google Scholar]
  • 85.Dobrovic A, Simpfendorfer D. Methylation of the BRCA1 gene in sporadic breast cancer. Cancer Res. 1997;57:3347–50. [PubMed] [Google Scholar]
  • 86.Antequera F. Genomic specification and epigenetic regulation of eukaryotic DNA replication origins. EMBO J. 2004;23:4365–70. doi: 10.1038/sj.emboj.7600450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 87.Sanchez-Elsner T, Gou D, Kremmer E, Sauer F. Noncoding RNAs of Trithorax response elements recruit Drosophila Ash1 to Ultrabithorax. Science. 2006;311:1118–23. doi: 10.1126/science.1117705. [DOI] [PubMed] [Google Scholar]
  • 88.Grimaud C, Bantignies F, Pal-Bhadra M, Ghana P, Bhadra U, Cavalli G. RNAi components are required for nuclear clustering of Polycomb group response elements. Cell. 2006;124:957–71. doi: 10.1016/j.cell.2006.01.036. [DOI] [PubMed] [Google Scholar]

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