1932

Abstract

Cancer arises from genetic alterations that produce dysregulated gene expression programs. Normal gene regulation occurs in the context of chromosome loop structures called insulated neighborhoods, and recent studies have shown that these structures are altered and can contribute to oncogene dysregulation in various cancer cells. We review the types of genetic and epigenetic alterations that influence neighborhood structures and contribute to gene dysregulation in cancer, present models for insulated neighborhoods associated with the most prominent human oncogenes, and discuss how such models may lead to further advances in cancer diagnosis and therapy.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-030617-050134
2018-03-04
2024-05-23
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/2/1/annurev-cancerbio-030617-050134.html?itemId=/content/journals/10.1146/annurev-cancerbio-030617-050134&mimeType=html&fmt=ahah

Literature Cited

  1. Armstrong SA, Look AT. 2005. Molecular genetics of acute lymphoblastic leukemia. J. Clin. Oncol. 23:6306–15 [Google Scholar]
  2. Balbás-Martínez C, Sagrera A, Carrillo-de-Santa-Pau E, Earl J, Márquez M. et al. 2013. Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy. Nat. Genet. 45:1464–69 [Google Scholar]
  3. Baniahmad A, Steiner C, Kohne AC, Renkawitz R. 1990. Modular structure of a chicken lysozyme silencer: involvement of an unusual thyroid hormone receptor binding site. Cell 61:505–14 [Google Scholar]
  4. Barber TD, McManus K, Yuen KW, Reis M, Parmigiani G. et al. 2008. Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers. PNAS 105:3443–48 [Google Scholar]
  5. Bell AC, Felsenfeld G. 2000. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405:482–85 [Google Scholar]
  6. Bell AC, West AG, Felsenfeld G. 1999. The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 98:387–96 [Google Scholar]
  7. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S. et al. 2010. The landscape of somatic copy-number alteration across human cancers. Nature 463:899–905 [Google Scholar]
  8. Bickmore WA, van Steensel B. 2013. Genome architecture: domain organization of interphase chromosomes. Cell 152:1270–84 [Google Scholar]
  9. Bonev B, Cavalli G. 2016. Organization and function of the 3D genome. Nat. Rev. Genet. 17:661–78 [Google Scholar]
  10. Bos JL. 1989. ras oncogenes in human cancer: a review. Cancer Res 49:4682–89 [Google Scholar]
  11. Boveri T. 1914. Zur Frage der Entstehung maligner Tumoren Jena, Ger: Gustav Fischer
  12. Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H. et al. 2013. The somatic genomic landscape of glioblastoma. Cell 155:462–77 [Google Scholar]
  13. Bunting KL, Soong TD, Singh R, Jiang Y, Beguelin W. et al. 2016. Multi-tiered reorganization of the genome during B cell affinity maturation anchored by a germinal center-specific locus control region. Immunity 45:497–512 [Google Scholar]
  14. Cancer Genome Atlas Res. Netw. 2013. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368:2059–74 [Google Scholar]
  15. Cancer Genome Atlas Res. Netw. 2014. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507:315–22 [Google Scholar]
  16. Cancer Genome Atlas Res. Netw. 2015. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N. Engl. J. Med. 372:2481–98 [Google Scholar]
  17. Cancer Genome Atlas Res. Netw. 2016. Comprehensive molecular characterization of papillary renal-cell carcinoma. N. Engl. J. Med. 374:135–45 [Google Scholar]
  18. Cavalli G, Misteli T. 2013. Functional implications of genome topology. Nat. Struct. Mol. Biol. 20:290–99 [Google Scholar]
  19. Corces MR, Corces VG. 2016. The three-dimensional cancer genome. Curr. Opin. Genet. Dev. 36:1–7 [Google Scholar]
  20. Cremer T, Cremer M. 2010. Chromosome territories. Cold Spring Harb. Perspect. Biol. 2:a003889 [Google Scholar]
  21. Crompton BD, Stewart C, Taylor-Weiner A, Alexe G, Kurek KC. et al. 2014. The genomic landscape of pediatric Ewing sarcoma. Cancer Discov 4:1326–41 [Google Scholar]
  22. Dang L, White DW, Gross S, Bennett BD, Bittinger MA. et al. 2009. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–44 [Google Scholar]
  23. de Laat W, Duboule D. 2013. Topology of mammalian developmental enhancers and their regulatory landscapes. Nature 502:499–506 [Google Scholar]
  24. Deardorff MA, Bando M, Nakato R, Watrin E, Itoh T. et al. 2012. HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature 489:313–17 [Google Scholar]
  25. Dekker J, Heard E. 2015. Structural and functional diversity of Topologically Associating Domains. FEBS Lett 589:2877–84 [Google Scholar]
  26. Dekker J, Mirny L. 2016. The 3D genome as moderator of chromosomal communication. Cell 164:1110–21 [Google Scholar]
  27. DeMare LE, Leng J, Cotney J, Reilly SK, Yin J. et al. 2013. The genomic landscape of cohesin-associated chromatin interactions. Genome Res 23:1224–34 [Google Scholar]
  28. Dixon JR, Gorkin DU, Ren B. 2016. Chromatin domains: the unit of chromosome organization. Mol. Cell 62:668–80 [Google Scholar]
  29. Dixon JR, Jung I, Selvaraj S, Shen Y, Antosiewicz-Bourget JE. et al. 2015. Chromatin architecture reorganization during stem cell differentiation. Nature 518:331–36 [Google Scholar]
  30. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y. et al. 2012. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:376–80 [Google Scholar]
  31. Dorsett D, Merkenschlager M. 2013. Cohesin at active genes: a unifying theme for cohesin and gene expression from model organisms to humans. Curr. Opin. Cell Biol. 25:327–333 [Google Scholar]
  32. Dowen JM, Bilodeau S, Orlando DA, Hubner MR, Abraham BJ. et al. 2013. Multiple structural maintenance of chromosome complexes at transcriptional regulatory elements. Stem Cell Rep 1:371–78 [Google Scholar]
  33. Dowen JM, Fan ZP, Hnisz D, Ren G, Abraham BJ. et al. 2014. Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes. Cell 159:374–87 [Google Scholar]
  34. Downward J. 2003. Targeting RAS signalling pathways in cancer therapy. Nat. Rev. Cancer 3:11–22 [Google Scholar]
  35. ENCODE Project Consortium. 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74 [Google Scholar]
  36. Filippova GN, Lindblom A, Meincke LJ, Klenova EM, Neiman PE. 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 Chromosom. Cancer 22:26–36 [Google Scholar]
  37. Filippova GN, Qi CF, Ulmer JE, Moore JM, Ward MD. et al. 2002. Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter its DNA-binding specificity. Cancer Res 62:48–52 [Google Scholar]
  38. Flavahan WA, Drier Y, Liau BB, Gillespie SM, Venteicher AS. et al. 2016. Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature 529:110–14 [Google Scholar]
  39. Fudenberg G, Imakaev M, Lu C, Goloborodko A, Abdennur N, Mirny LA. 2016. Formation of chromosomal domains by loop extrusion. Cell Rep 15:2038–49 [Google Scholar]
  40. Ghirlando R, Felsenfeld G. 2016. CTCF: making the right connections. Genes Dev 30:881–91 [Google Scholar]
  41. Gibcus JH, Dekker J. 2013. The hierarchy of the 3D genome. Mol. Cell 49:773–82 [Google Scholar]
  42. Giorgetti L, Galupa R, Nora EP, Piolot T, Lam F. et al. 2014. Predictive polymer modeling reveals coupled fluctuations in chromosome conformation and transcription. Cell 157:950–63 [Google Scholar]
  43. Gorkin DU, Leung D, Ren B. 2014. The 3D genome in transcriptional regulation and pluripotency. Cell Stem Cell 14:762–75 [Google Scholar]
  44. Groschel S, Sanders MA, Hoogenboezem R, de Wit E, Bouwman BA. et al. 2014. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell 157:369–81 [Google Scholar]
  45. Guo G, Sun X, Chen C, Wu S, Huang P. et al. 2013. Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nat. Genet. 45:1459–63 [Google Scholar]
  46. Guo Y, Xu Q, Canzio D, Shou J, Li J. et al. 2015. CRISPR inversion of CTCF sites alters genome topology and enhancer/promoter function. Cell 162:900–10 [Google Scholar]
  47. Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U. et al. 2014. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 28:241–47 [Google Scholar]
  48. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ. et al. 2013. Safety and tumor responses with lambrolizumab (anti–PD-1) in melanoma. N. Engl. J. Med. 369:134–44 [Google Scholar]
  49. Handoko L, Xu H, Li G, Ngan CY, Chew E. et al. 2011. CTCF-mediated functional chromatin interactome in pluripotent cells. Nat. Genet. 43:630–38 [Google Scholar]
  50. Hansen AS, Pustova I, Cattoglio C, Tjian R, Darzacq X. 2017. CTCF and cohesin regulate chromatin loop stability with distinct dynamics. eLife 6:e25776 [Google Scholar]
  51. Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM. 2000. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405:486–89 [Google Scholar]
  52. Hirano T. 2006. At the heart of the chromosome: SMC proteins in action. Nat. Rev. Mol. Cell Biol. 7:311–22 [Google Scholar]
  53. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V. et al. 2013. Super-enhancers in the control of cell identity and disease. Cell 155:934–47 [Google Scholar]
  54. Hnisz D, Day DS, Young RA. 2016.a Insulated neighborhoods: structural and functional units of mammalian gene control. Cell 167:1188–200 [Google Scholar]
  55. Hnisz D, Weintraub AS, Day DS, Valton AL, Bak RO. et al. 2016.b Activation of proto-oncogenes by disruption of chromosome neighborhoods. Science 351:1454–58 [Google Scholar]
  56. Hou C, Zhao H, Tanimoto K, Dean A. 2008. CTCF-dependent enhancer-blocking by alternative chromatin loop formation. PNAS 105:20398–403 [Google Scholar]
  57. Imakaev M, Fudenberg G, McCord RP, Naumova N, Goloborodko A. et al. 2012. Iterative correction of Hi-C data reveals hallmarks of chromosome organization. Nat. Methods 9:999–1003 [Google Scholar]
  58. Ji X, Dadon DB, Powell BE, Fan ZP, Borges-Rivera D. et al. 2016. 3D chromosome regulatory landscape of human pluripotent cells. Cell Stem Cell 18:262–75 [Google Scholar]
  59. Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA. et al. 2010. Mediator and cohesin connect gene expression and chromatin architecture. Nature 467:430–35 [Google Scholar]
  60. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B. et al. 2013. Mutational landscape and significance across 12 major cancer types. Nature 502:333–39 [Google Scholar]
  61. Kanduri C, Pant V, Loukinov D, Pugacheva E, Qi CF. et al. 2000. Functional association of CTCF with the insulator upstream of the H19 gene is parent of origin-specific and methylation-sensitive. Curr. Biol. 10:853–56 [Google Scholar]
  62. Katainen R, Dave K, Pitkanen E, Palin K, Kivioja T. et al. 2015. CTCF/cohesin-binding sites are frequently mutated in cancer. Nat. Genet. 47:818–21 [Google Scholar]
  63. Kemp CJ, Moore JM, Moser R, Bernard B, Teater M. et al. 2014. CTCF haploinsufficiency destabilizes DNA methylation and predisposes to cancer. Cell Rep 7:1020–29 [Google Scholar]
  64. Kihara R, Nagata Y, Kiyoi H, Kato T, Yamamoto E. et al. 2014. Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia 28:1586–95 [Google Scholar]
  65. Kim TH, Abdullaev ZK, Smith AD, Ching KA, Loukinov DI. et al. 2007. Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome. Cell 128:1231–45 [Google Scholar]
  66. Kon A, Shih LY, Minamino M, Sanada M, Shiraishi Y. et al. 2013. Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. Nat. Genet. 45:1232–37 [Google Scholar]
  67. Krijger PH, de Laat W. 2016. Regulation of disease-associated gene expression in the 3D genome. Nat. Rev. Mol. Cell Biol. 17:771–82 [Google Scholar]
  68. Kung JT, Kesner B, An JY, Ahn JY, Cifuentes-Rojas C. et al. 2015. Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF. Mol. Cell 57:361–75 [Google Scholar]
  69. Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA. et al. 2014. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505:495–501 [Google Scholar]
  70. Lefevre P, Witham J, Lacroix CE, Cockerill PN, Bonifer C. 2008. The LPS-induced transcriptional upregulation of the chicken lysozyme locus involves CTCF eviction and noncoding RNA transcription. Mol. Cell 32:129–39 [Google Scholar]
  71. Lin CP, He L. 2017. Noncoding RNAs in cancer development. Annu. Rev. Cancer Biol. 1:163–84 [Google Scholar]
  72. Lindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S. et al. 2015. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 125:1267–76 [Google Scholar]
  73. Liu M, Maurano MT, Wang H, Qi H, Song CZ. et al. 2015. Genomic discovery of potent chromatin insulators for human gene therapy. Nat. Biotechnol. 33:198–203 [Google Scholar]
  74. Liu XS, Wu H, Ji X, Stelzer Y, Wu X. et al. 2016. Editing DNA methylation in the mammalian genome. Cell 167:233–47.e217 [Google Scholar]
  75. Lobanenkov VV, Nicolas RH, Adler VV, Paterson H, Klenova EM. et al. 1990. A novel sequence-specific DNA binding protein which interacts with three regularly spaced direct repeats of the CCCTC-motif in the 5′-flanking sequence of the chicken c-myc gene. Oncogene 5:1743–53 [Google Scholar]
  76. Loukinov DI, Pugacheva E, Vatolin S, Pack SD, Moon H. et al. 2002. 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. PNAS 99:6806–11 [Google Scholar]
  77. Lupianez DG, Kraft K, Heinrich V, Krawitz P, Brancati F. et al. 2015. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161:1012–15 [Google Scholar]
  78. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA. et al. 2004. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib. N. Engl. J. Med. 350:2129–39 [Google Scholar]
  79. Mazumdar C, Shen Y, Xavy S, Zhao F, Reinisch A. et al. 2015. Leukemia-associated cohesin mutants dominantly enforce stem cell programs and impair human hematopoietic progenitor differentiation. Cell Stem Cell 17:675–88 [Google Scholar]
  80. Merkenschlager M, Nora EP. 2016. CTCF and cohesin in genome folding and transcriptional gene regulation. Annu. Rev. Genom. Hum. Genet. 17:17–43 [Google Scholar]
  81. Merkenschlager M, Odom DT. 2013. CTCF and cohesin: linking gene regulatory elements with their targets. Cell 152:1285–97 [Google Scholar]
  82. Mukhopadhyay R, Yu W, Whitehead J, Xu J, Lezcano M. et al. 2004. The binding sites for the chromatin insulator protein CTCF map to DNA methylation-free domains genome-wide. Genome Res 14:1594–602 [Google Scholar]
  83. Mullenders J, Aranda-Orgilles B, Lhoumaud P, Keller M, Pae J. et al. 2015. Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms. J. Exp. Med. 212:1833–50 [Google Scholar]
  84. Narendra V, Rocha PP, An D, Raviram R, Skok JA. et al. 2015. CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation. Science 347:1017–21 [Google Scholar]
  85. Nasmyth K, Haering CH. 2009. Cohesin: its roles and mechanisms. Annu. Rev. Genet. 43:525–58 [Google Scholar]
  86. Naumova N, Imakaev M, Fudenberg G, Zhan Y, Lajoie BR. et al. 2013. Organization of the mitotic chromosome. Science 342:948–53 [Google Scholar]
  87. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I. et al. 2012. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485:381–85 [Google Scholar]
  88. Nowell PC, Hungerford DA. 1960. Chromosome studies on normal and leukemic human leukocytes. J. Natl. Cancer Inst. 25:85–109 [Google Scholar]
  89. Oldridge DA, Wood AC, Weichert-Leahey N, Crimmins I, Sussman R. et al. 2015. Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism. Nature 528:418–21 [Google Scholar]
  90. Ong CT, Corces VG. 2014. CTCF: an architectural protein bridging genome topology and function. Nat. Rev. Genet. 15:234–46 [Google Scholar]
  91. Palstra RJ, Tolhuis B, Splinter E, Nijmeijer R, Grosveld F, de Laat W. 2003. The β-globin nuclear compartment in development and erythroid differentiation. Nat. Genet. 35:190–94 [Google Scholar]
  92. Pardoll DM. 2012. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12:252–64 [Google Scholar]
  93. Parelho V, Hadjur S, Spivakov M, Leleu M, Sauer S. et al. 2008. Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell 132:422–33 [Google Scholar]
  94. Phillips JE, Corces VG. 2009. CTCF: master weaver of the genome. Cell 137:1194–211 [Google Scholar]
  95. Phillips-Cremins JE, Corces VG. 2013. Chromatin insulators: linking genome organization to cellular function. Mol. Cell 50:461–74 [Google Scholar]
  96. Phillips-Cremins JE, Sauria ME, Sanyal A, Gerasimova TI, Lajoie BR. et al. 2013. Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell 153:1281–95 [Google Scholar]
  97. Poulos RC, Thoms JA, Guan YF, Unnikrishnan A, Pimanda JE, Wong JW. 2016. Functional mutations form at CTCF-cohesin binding sites in melanoma due to uneven nucleotide excision repair across the motif. Cell Rep 17:2865–72 [Google Scholar]
  98. Price JC, Pollock LM, Rudd ML, Fogoros SK, Mohamed H. et al. 2014. Sequencing of candidate chromosome instability genes in endometrial cancers reveals somatic mutations in ESCO1, CHTF18, and MRE11A. PLOS ONE 8:e63313 [Google Scholar]
  99. Rabbitts TH. 1994. Chromosomal translocations in human cancer. Nature 372:143–49 [Google Scholar]
  100. Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID. et al. 2014. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159:1665–80 [Google Scholar]
  101. Rubio ED, Reiss DJ, Welcsh PL, Disteche CM, Filippova GN. et al. 2008. CTCF physically links cohesin to chromatin. PNAS 105:8309–14 [Google Scholar]
  102. Saldaña-Meyer R, González-Buendía E, Guerrero G, Narendra V, Bonasio R. et al. 2014. CTCF regulates the human p53 gene through direct interaction with its natural antisense transcript, Wrap53. Genes Dev 28:723–34 [Google Scholar]
  103. Sanborn AL, Rao SS, Huang SC, Durand NC, Huntley MH. et al. 2015. Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. PNAS 112:E6456–65 [Google Scholar]
  104. Seitan VC, Hao B, Tachibana-Konwalski K, Lavagnolli T, Mira-Bontenbal H. et al. 2011. A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation. Nature 476:467–71 [Google Scholar]
  105. Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ. 2005. Cancer/testis antigens, gametogenesis and cancer. Nat. Rev. Cancer 5:615–25 [Google Scholar]
  106. Solomon DA, Kim JS, Bondaruk J, Shariat SF, Wang ZF. et al. 2013. Frequent truncating mutations of STAG2 in bladder cancer. Nat. Genet. 45:1428–30 [Google Scholar]
  107. Splinter E, Heath H, Kooren J, Palstra RJ, Klous P. et al. 2006. CTCF mediates long-range chromatin looping and local histone modification in the β-globin locus. Genes Dev 20:2349–54 [Google Scholar]
  108. Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C. et al. 2012. The landscape of cancer genes and mutational processes in breast cancer. Nature 486:400–4 [Google Scholar]
  109. Sun S, Del Rosario BC, Szanto A, Ogawa Y, Jeon Y, Lee JT. 2013. Jpx RNA activates Xist by evicting CTCF. Cell 153:1537–51 [Google Scholar]
  110. Szabo P, Tang SH, Rentsendorj A, Pfeifer GP, Mann JR. 2000. Maternal-specific footprints at putative CTCF sites in the H19 imprinting control region give evidence for insulator function. Curr. Biol. 10:607–10 [Google Scholar]
  111. Tang Z, Luo OJ, Li X, Zheng M, Zhu JJ. et al. 2015. CTCF-mediated human 3D genome architecture reveals chromatin topology for transcription. Cell 163:1611–27 [Google Scholar]
  112. Taylor CF, Platt FM, Hurst CD, Thygesen HH, Knowles MA. 2014. Frequent inactivating mutations of STAG2 in bladder cancer are associated with low tumour grade and stage and inversely related to chromosomal copy number changes. Hum. Mol. Genet. 15:1964–74 [Google Scholar]
  113. Tedeschi A, Wutz G, Huet S, Jaritz M, Wuensche A. et al. 2013. Wapl is an essential regulator of chromatin structure and chromosome segregation. Nature 501:564–68 [Google Scholar]
  114. Thota S, Viny AD, Makishima H, Spitzer B, Radivoyevitch T. et al. 2014. Genetic alterations of the cohesin complex genes in myeloid malignancies. Blood 124:1790–98 [Google Scholar]
  115. Tirode F, Surdez D, Ma X, Parker M, Le Deley MC. et al. 2014. Genomic landscapes of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov 4:1342–53 [Google Scholar]
  116. Tolhuis B, Palstra RJ, Splinter E, Grosveld F, de Laat W. 2002. Looping and interaction between hypersensitive sites in the active β-globin locus. Mol. Cell 10:1453–65 [Google Scholar]
  117. Uhlmann F. 2016. SMC complexes: from DNA to chromosomes. Nat. Rev. Mol. Cell Biol. 17:399–412 [Google Scholar]
  118. Umer HM, Cavalli M, Dabrowski MJ, Diamanti K, Kruczyk M. et al. 2016. A significant regulatory mutation burden at a high-affinity position of the CTCF motif in gastrointestinal cancers. Hum. Mutat. 37:904–13 [Google Scholar]
  119. Valton AL, Dekker J. 2016. TAD disruption as oncogenic driver. Curr. Opin. Genet. Dev. 36:34–40 [Google Scholar]
  120. Van Vlierberghe P, Ferrando A. 2012. The molecular basis of T cell acute lymphoblastic leukemia. J. Clin. Investig. 122:3398–406 [Google Scholar]
  121. Viny AD, Ott CJ, Spitzer B, Rivas M, Meydan C. et al. 2015. Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis. J. Exp. Med. 212:1819–32 [Google Scholar]
  122. Vogelstein B, Kinzler KW. 2004. Cancer genes and the pathways they control. Nat. Med. 10:789–99 [Google Scholar]
  123. Walker CJ, Miranda MA, O'Hern MJ, McElroy JP, Coombes KR. et al. 2015. Patterns of CTCF and ZFHX3 mutation and associated outcomes in endometrial cancer. J. Natl. Cancer Inst. 107:djv249 [Google Scholar]
  124. Walter MJ, Shen D, Shao J, Ding L, White BS. et al. 2013. Clonal diversity of recurrently mutated genes in myelodysplastic syndromes. Leukemia 27:1275–82 [Google Scholar]
  125. Wang H, Maurano MT, Qu H, Varley KE, Gertz J. et al. 2012. Widespread plasticity in CTCF occupancy linked to DNA methylation. Genome Res 22:1680–88 [Google Scholar]
  126. Wendt KS, Yoshida K, Itoh T, Bando M, Koch B. et al. 2008. Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature 451:796–801 [Google Scholar]
  127. Xiao T, Wallace J, Felsenfeld G. 2011. Specific sites in the C terminus of CTCF interact with the SA2 subunit of the cohesin complex and are required for cohesin-dependent insulation activity. Mol. Cell. Biol. 31:2174–83 [Google Scholar]
  128. Yu W, Ginjala V, Pant V, Chernukhin I, Whitehead J. et al. 2004. Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation. Nat. Genet. 36:1105–10 [Google Scholar]
  129. Yusufzai TM, Tagami H, Nakatani Y, Felsenfeld G. 2004. CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol. Cell 13:291–98 [Google Scholar]
  130. Zuin J, Dixon JR, van der Reijden MI, Ye Z, Kolovos P. et al. 2014. Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells. PNAS 111:996–1001 [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-030617-050134
Loading
/content/journals/10.1146/annurev-cancerbio-030617-050134
Loading

Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error