SpringerLink
Log in

Epigenetics of Inflammatory Bowel Disease

  • Chapter
  • First Online:
Molecular Genetics of Inflammatory Bowel Disease

  • 1061 Accesses

Abstract

The term epigenome refers to the tissue- and cell-type-specific collection of DNA methylation, histone modifications, and chromatin accessibility and the set of coding and noncoding RNA molecules (Bernstein et al., Cell 125:315–326, 2006) that are dynamically modulated throughout the lifetime of an individual. Epigenetic modifications are critical for regular developmental processes in the intestine, but variation in the epigenome has also been associated with the development of intestinal diseases, including inflammatory bowel disease (Vavricka et al., Inflammatory Bowel Diseases 17:1530–1539, 2011). We hypothesize that plasticity of the epigenome in different cellular compartments links genetic susceptibility and environmental influences and may determine “decision points” in the progression towards disease onset (i.e., manifestation) and/or progression of IBD. This chapter reviews selected aspects of IBD research with the aim to link the current knowledge of genetic, epigenetic, and functional studies into an integrated view on the role of epigenetic variation in intestinal inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (Brazil)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (Brazil)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (Brazil)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Bernstein BE, Mikkelsen TS, **e X, Kamal M, Huebert DJ, Cuff J et al (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125(2):315–326, Epub 2006/04/25

    Article  PubMed  CAS  Google Scholar 

  2. Waddington CH (2012) The epigenotype. 1942. Int J Epidemiol 41(1):10–13

    Article  PubMed  CAS  Google Scholar 

  3. Gendrel AV, Heard E (2011) Fifty years of X-inactivation research. Development 138(23):5049–5055, Epub 2011/11/10

    Article  PubMed  CAS  Google Scholar 

  4. Ferguson-Smith AC (2011) Genomic imprinting: the emergence of an epigenetic paradigm. Nat Rev Genet 12(8):565–575, Epub 2011/07/19

    Article  PubMed  CAS  Google Scholar 

  5. Reik W (2007) Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447(7143):425–432, Epub 2007/05/25

    Article  PubMed  CAS  Google Scholar 

  6. Cherry AB, Daley GQ (2012) Reprogramming cellular identity for regenerative medicine. Cell 148(6):1110–1122, Epub 2012/03/20

    Article  PubMed  CAS  Google Scholar 

  7. Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301(5895):89–92, Epub 1983/01/06

    Article  PubMed  CAS  Google Scholar 

  8. Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature 447(7143):433–440, Epub 2007/05/25

    Article  PubMed  CAS  Google Scholar 

  9. Petronis A (2010) Epigenetics as a unifying principle in the aetiology of complex traits and diseases. Nature 465(7299):721–727, Epub 2010/06/11

    Article  PubMed  CAS  Google Scholar 

  10. Bird A (2007) Perceptions of epigenetics. Nature 447(7143):396–398, Epub 2007/05/25

    Article  PubMed  CAS  Google Scholar 

  11. Suzuki MM, Bird A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9(6):465–476, Epub 2008/05/09

    Article  PubMed  CAS  Google Scholar 

  12. Branco MR, Ficz G, Reik W (2012) Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat Rev Genet 13(1):7–13, Epub 2011/11/16

    CAS  Google Scholar 

  13. Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21(3):381–395, Epub 2011/02/16

    Article  PubMed  CAS  Google Scholar 

  14. Rakyan VK, Down TA, Balding DJ, Beck S (2011) Epigenome-wide association studies for common human diseases. Nat Rev Genet 12(8):529–541, Epub 2011/07/13

    Article  PubMed  CAS  Google Scholar 

  15. Visscher PM, Brown MA, McCarthy MI, Yang J (2012) Five years of GWAS discovery. Am J Hum Genet 90(1):7–24, Epub 2012/01/17

    Article  PubMed  CAS  Google Scholar 

  16. Beck S (2010) Taking the measure of the methylome. Nat Biotechnol 28(10):1026–1028, Epub 2010/10/15

    Article  PubMed  CAS  Google Scholar 

  17. Laird PW (2010) Principles and challenges of genomewide DNA methylation analysis. Nat Rev Genet 11(3):191–203, Epub 2010/02/04

    Article  PubMed  CAS  Google Scholar 

  18. Rakyan VK, Beyan H, Down TA, Hawa MI, Maslau S, Aden D et al (2011) Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. PLoS Genet 7(9):e1002300, Epub 2011/10/08

    Article  PubMed  CAS  Google Scholar 

  19. Bell JT, Spector TD (2011) A twin approach to unraveling epigenetics. Trends Genet 27(3):116–125, Epub 2011/01/25

    Article  PubMed  CAS  Google Scholar 

  20. Schreiber S, Rosenstiel P, Albrecht M, Hampe J, Krawczak M (2005) Genetics of Crohn disease, an archetypal inflammatory barrier disease. Nat Rev Genet 6(5):376–388, Epub 2005/04/30

    Article  PubMed  CAS  Google Scholar 

  21. Felsen J, Wolarsky W (1955) Familial incidence of ulcerative colitis and ileitis. Gastroenterology 28(3):412–417, Epub 1955/03/01

    PubMed  CAS  Google Scholar 

  22. Rosenstiel P, Sina C, Franke A, Schreiber S (2009) Towards a molecular risk map—recent advances on the etiology of inflammatory bowel disease. Semin Immunol 21(6):334–345, Epub 2009/11/21

    Article  PubMed  CAS  Google Scholar 

  23. Hampe J, Cuthbert A, Croucher PJ, Mirza MM, Mascheretti S, Fisher S et al (2001) Association between insertion mutation in NOD2 gene and Crohn’s disease in German and British populations. Lancet 357(9272):1925–1928, Epub 2001/06/27

    Article  PubMed  CAS  Google Scholar 

  24. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J et al (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411(6837):599–603, Epub 2001/06/01

    Article  PubMed  CAS  Google Scholar 

  25. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ et al (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314(5804):1461–1463, Epub 2006/10/28

    Article  PubMed  CAS  Google Scholar 

  26. Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T et al (2008) Replication of signals from recent studies of Crohn’s disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet 40(6):713–715, Epub 2008/04/29

    Article  PubMed  CAS  Google Scholar 

  27. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491(7422):119–124, Epub 2012/11/07

    Article  PubMed  CAS  Google Scholar 

  28. Orholm M, Binder V, Sorensen TI, Rasmussen LP, Kyvik KO (2000) Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study. Scand J Gastroenterol 35(10):1075–1081, Epub 2000/12/01

    Article  PubMed  CAS  Google Scholar 

  29. Maher B (2008) Personal genomes: the case of the missing heritability. Nature 456(7218):18–21, Epub 2008/11/07

    Article  PubMed  CAS  Google Scholar 

  30. Renz H, von Mutius E, Brandtzaeg P, Cookson WO, Autenrieth IB, Haller D (2011) Gene-environment interactions in chronic inflammatory disease. Nat Immunol 12(4):273–277, Epub 2011/03/23

    Article  PubMed  CAS  Google Scholar 

  31. Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429(6990):457–463, Epub 2004/05/28

    Article  PubMed  CAS  Google Scholar 

  32. Goelz SE, Vogelstein B, Hamilton SR, Feinberg AP (1985) Hypomethylation of DNA from benign and malignant human colon neoplasms. Science 228(4696):187–190, Epub 1985/04/12

    Article  PubMed  CAS  Google Scholar 

  33. Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8(4):286–298, Epub 2007/03/07

    Article  PubMed  CAS  Google Scholar 

  34. Melo SA, Ropero S, Moutinho C, Aaltonen LA, Yamamoto H, Calin GA et al (2009) A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nat Genet 41(3):365–370, Epub 2009/02/17

    Article  PubMed  CAS  Google Scholar 

  35. Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA et al (2006) Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 9(6):435–443, Epub 2006/06/13

    Article  PubMed  CAS  Google Scholar 

  36. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES et al (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 105(44):17046–17049, Epub 2008/10/29

    Article  PubMed  CAS  Google Scholar 

  37. Mann MR, Lee SS, Doherty AS, Verona RI, Nolen LD, Schultz RM et al (2004) Selective loss of imprinting in the placenta following preimplantation development in culture. Development 131(15):3727–3735, Epub 2004/07/09

    Article  PubMed  CAS  Google Scholar 

  38. Rakyan VK, Down TA, Thorne NP, Flicek P, Kulesha E, Graf S et al (2008) An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res 18(9):1518–1529, Epub 2008/06/26

    Article  PubMed  CAS  Google Scholar 

  39. van Overveld FJ, Demkow UA, Gorecka D, Zielinski J, De Backer WA (2003) Inhibitory capacity of different steroids on neutrophil migration across a bilayer of endothelial and bronchial epithelial cells. Eur J Pharmacol 477(3):261–267, Epub 2003/10/03

    Article  PubMed  Google Scholar 

  40. Backdahl L, Bushell A, Beck S (2009) Inflammatory signalling as mediator of epigenetic modulation in tissue-specific chronic inflammation. Int J Biochem Cell Biol 41(1):176–184, Epub 2008/09/17

    Article  PubMed  CAS  Google Scholar 

  41. Shuto T, Furuta T, Oba M, Xu H, Li JD, Cheung J et al (2006) Promoter hypomethylation of Toll-like receptor-2 gene is associated with increased proinflammatory response toward bacterial peptidoglycan in cystic fibrosis bronchial epithelial cells. FASEB J 20(6):782–784, Epub 2006/02/16

    PubMed  CAS  Google Scholar 

  42. Barros SP, Offenbacher S (2009) Epigenetics: connecting environment and genotype to phenotype and disease. J Dent Res 88(5):400–408, Epub 2009/06/06

    Article  PubMed  CAS  Google Scholar 

  43. Gervin K, Vigeland MD, Mattingsdal M, Hammero M, Nygard H, Olsen AO et al (2012) DNA methylation and gene expression changes in monozygotic twins discordant for psoriasis: identification of epigenetically dysregulated genes. PLoS Genet 8(1):e1002454, Epub 2012/02/01

    Article  PubMed  CAS  Google Scholar 

  44. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20, Epub 2005/01/18

    Article  PubMed  CAS  Google Scholar 

  45. Nahid MA, Pauley KM, Satoh M, Chan EK (2009) miR-146a is critical for endotoxin-induced tolerance: IMPLICATION IN INNATE IMMUNITY. J Biol Chem 284(50):34590–34599, Epub 2009/10/21

    Article  PubMed  CAS  Google Scholar 

  46. Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 103(33):12481–12486, Epub 2006/08/04

    Article  PubMed  CAS  Google Scholar 

  47. Gloria L, Cravo M, Pinto A, de Sousa LS, Chaves P, Leitao CN et al (1996) DNA hypomethylation and proliferative activity are increased in the rectal mucosa of patients with long-standing ulcerative colitis. Cancer 78(11):2300–2306, Epub 1996/12/01

    Article  PubMed  CAS  Google Scholar 

  48. Kellermayer R, Balasa A, Zhang W, Lee S, Mirza S, Chakravarty A et al (2010) Epigenetic maturation in colonic mucosa continues beyond infancy in mice. Hum Mol Genet 19(11):2168–2176, Epub 2010/03/04

    Article  PubMed  CAS  Google Scholar 

  49. Gonsky R, Deem RL, Targan SR (2009) Distinct methylation of IFNG in the gut. J Interferon Cytokine Res 29(7):407–414, Epub 2009/05/20

    Article  PubMed  CAS  Google Scholar 

  50. Gonsky R, Deem RL, Landers CJ, Derkowski CA, Berel D, McGovern DP et al (2011) Distinct IFNG methylation in a subset of ulcerative colitis patients based on reactivity to microbial antigens. Inflamm Bowel Dis 17(1):171–178, Epub 2010/09/18

    Article  PubMed  Google Scholar 

  51. Dideberg V, Kristjansdottir G, Milani L, Libioulle C, Sigurdsson S, Louis E et al (2007) An insertion-deletion polymorphism in the interferon regulatory factor 5 (IRF5) gene confers risk of inflammatory bowel diseases. Hum Mol Genet 16(24):3008–3016, Epub 2007/09/21

    Article  PubMed  CAS  Google Scholar 

  52. Balasa A, Gathungu G, Kisfali P, Smith EO, Cho JH, Melegh B et al (2010) Assessment of DNA methylation at the interferon regulatory factor 5 (IRF5) promoter region in inflammatory bowel diseases. Int J Colorectal Dis 25(5):553–556, Epub 2010/02/04

    Article  PubMed  Google Scholar 

  53. Lin Z, Hegarty JP, Cappel JA, Yu W, Chen X, Faber P et al (2011) Identification of disease-associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease. Clin Genet 80(1):59–67, Epub 2010/10/19

    Article  PubMed  CAS  Google Scholar 

  54. Nimmo ER, Prendergast JG, Aldhous MC, Kennedy NA, Henderson P, Drummond HE et al (2012) Genome-wide methylation profiling in Crohn’s disease identifies altered epigenetic regulation of key host defense mechanisms including the Th17 pathway. Inflamm Bowel Dis 18(5):889–899, Epub 2011/10/25

    Article  PubMed  Google Scholar 

  55. Gore SD, Jones C, Kirkpatrick P (2006) Decitabine. Nat Rev Drug Discov 5(11):891–892, Epub 2006/11/23

    Article  PubMed  CAS  Google Scholar 

  56. Issa JP, Kantarjian HM, Kirkpatrick P (2005) Azacitidine. Nat Rev Drug Discov 4(4):275–276, Epub 2005/05/03

    Article  PubMed  CAS  Google Scholar 

  57. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854, Epub 1993/12/03

    Article  PubMed  CAS  Google Scholar 

  58. John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS (2004) Human microRNA targets. PLoS Biol 2(11):e363, Epub 2004/10/27

    Article  PubMed  Google Scholar 

  59. Sonkoly E, Wei T, Janson PC, Saaf A, Lundeberg L, Tengvall-Linder M et al (2007) MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One 2(7):e610, Epub 2007/07/12

    Article  PubMed  Google Scholar 

  60. Suarez Y, Wang C, Manes TD, Pober JS (2010) Cutting edge: TNF-induced microRNAs regulate TNF-induced expression of E-selectin and intercellular adhesion molecule-1 on human endothelial cells: feedback control of inflammation. J Immunol 184(1):21–25, Epub 2009/12/02

    Article  PubMed  CAS  Google Scholar 

  61. Worm J, Stenvang J, Petri A, Frederiksen KS, Obad S, Elmen J et al (2009) Silencing of microRNA-155 in mice during acute inflammatory response leads to derepression of c/ebp beta and down-regulation of G-CSF. Nucleic Acids Res 37(17):5784–5792, Epub 2009/07/15

    Article  PubMed  CAS  Google Scholar 

  62. Häsler R, Jacobs G, Till A, Grabe N, Cordes C, Nikolaus S, et al (2012) Microbial pattern recognition causes distinct functional microRNA signatures in human primary monocytes PLoS One.7(2):e31151. doi: 10.1371/journal.pone.0031151

    Google Scholar 

  63. Wu F, Zhang S, Dassopoulos T, Harris ML, Bayless TM, Meltzer SJ et al (2010) Identification of microRNAs associated with ileal and colonic Crohn’s disease. Inflamm Bowel Dis 16(10):1729–1738, Epub 2010/09/18

    Article  PubMed  Google Scholar 

  64. Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D et al (2011) Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis. J Clin Immunol 31(1):69–73, Epub 2010/09/18

    Article  PubMed  CAS  Google Scholar 

  65. Zwiers A, Kraal L, van de Pouw Kraan TC, Wurdinger T, Bouma G, Kraal G (2012) Cutting edge: a variant of the IL-23R gene associated with inflammatory bowel disease induces loss of microRNA regulation and enhanced protein production. J Immunol 188(4):1573–1577, Epub 2012/01/21

    Article  PubMed  CAS  Google Scholar 

  66. Duttagupta R, DiRienzo S, Jiang R, Bowers J, Gollub J, Kao J et al (2012) Genome-wide maps of circulating miRNA biomarkers for ulcerative colitis. PLoS One 7(2):e31241, Epub 2012/02/24

    Article  PubMed  CAS  Google Scholar 

  67. Fasseu M, Treton X, Guichard C, Pedruzzi E, Cazals-Hatem D, Richard C et al (2010) Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease. PLoS One 5(10):e13160, Epub 2010/10/20

    Article  PubMed  Google Scholar 

  68. Gent AE, Hellier MD, Grace RH, Swarbrick ET, Coggon D (1994) Inflammatory bowel disease and domestic hygiene in infancy. Lancet 343(8900):766–767, Epub 1994/03/26

    Article  PubMed  CAS  Google Scholar 

  69. Hampe J, Heymann K, Krawczak M, Schreiber S (2003) Association of inflammatory bowel disease with indicators for childhood antigen and infection exposure. Int J Colorectal Dis 18(5):413–417, Epub 2003/04/11

    Article  PubMed  Google Scholar 

  70. Dicksved J, Floistrup H, Bergstrom A, Rosenquist M, Pershagen G, Scheynius A et al (2007) Molecular fingerprinting of the fecal microbiota of children raised according to different lifestyles. Appl Environ Microbiol 73(7):2284–2289, Epub 2007/02/13

    Article  PubMed  CAS  Google Scholar 

  71. von Mutius E, Fritzsch C, Weiland SK, Roll G, Magnussen H (1992) Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison. BMJ 305(6866):1395–1399, Epub 1992/12/05

    Article  Google Scholar 

  72. von Mutius E, Martinez FD, Fritzsch C, Nicolai T, Reitmeir P, Thiemann HH (1994) Skin test reactivity and number of siblings. BMJ 308(6930):692–695, Epub 1994/03/12

    Article  Google Scholar 

  73. Cho I, Blaser MJ (2012) The human microbiome: at the interface of health and disease. Nat Rev Genet 13(4):260–270, Epub 2012/03/14

    PubMed  CAS  Google Scholar 

  74. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI (2007) The human microbiome project. Nature 449(7164):804–810, Epub 2007/10/19

    Article  PubMed  CAS  Google Scholar 

  75. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR et al (2011) Enterotypes of the human gut microbiome. Nature 473(7346):174–180, Epub 2011/04/22

    Article  PubMed  CAS  Google Scholar 

  76. Bamias G, Martin C 3rd, Marini M, Hoang S, Mishina M, Ross WG et al (2003) Expression, localization, and functional activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease. J Immunol 171(9):4868–4874

    PubMed  CAS  Google Scholar 

  77. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122):1027–1031, Epub 2006/12/22

    Article  PubMed  Google Scholar 

  78. Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M et al (2012) ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 487(7408):477–481, Epub 2012/07/28

    Article  PubMed  CAS  Google Scholar 

  79. Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A et al (2012) Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336(6080):489–493, Epub 2012/03/24

    Article  PubMed  CAS  Google Scholar 

  80. Lepage P, Hasler R, Spehlmann ME, Rehman A, Zvirbliene A, Begun A et al (2011) Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 141(1):227–236, Epub 2011/05/31

    Article  PubMed  Google Scholar 

  81. Barnett M, Bermingham E, McNabb W, Bassett S, Armstrong K, Rounce J et al (2010) Investigating micronutrients and epigenetic mechanisms in relation to inflammatory bowel disease. Mutat Res 690(1–2):71–80, Epub 2010/03/02

    PubMed  CAS  Google Scholar 

  82. Adams D, Altucci L, Antonarakis SE, Ballesteros J, Beck S, Bird A et al (2012) BLUEPRINT to decode the epigenetic signature written in blood. Nat Biotechnol 30(3):224–226, Epub 2012/03/09

    Article  PubMed  CAS  Google Scholar 

  83. Rajput S, Wilber A (2010) Roles of inflammation in cancer initiation, progression, and metastasis. Front Biosci (Schol Ed) 2:176–183, Epub 2009/12/29

    Article  Google Scholar 

  84. Chan AO, Rashid A (2006) CpG island methylation in precursors of gastrointestinal malignancies. Curr Mol Med 6(4):401–408, Epub 2006/08/12

    Article  PubMed  CAS  Google Scholar 

  85. Valinluck V, Sowers LC (2007) Inflammation-mediated cytosine damage: a mechanistic link between inflammation and the epigenetic alterations in human cancers. Cancer Res 67(12):5583–5586, Epub 2007/06/19

    Article  PubMed  CAS  Google Scholar 

  86. Azarschab P, Porschen R, Gregor M, Blin N, Holzmann K (2002) Epigenetic control of the E-cadherin gene (CDH1) by CpG methylation in colectomy samples of patients with ulcerative colitis. Genes Chromosomes Cancer 35(2):121–126, Epub 2002/08/31

    Article  PubMed  CAS  Google Scholar 

  87. Konishi K, Shen L, Wang S, Meltzer SJ, Harpaz N, Issa JP (2007) Rare CpG island methylator phenotype in ulcerative colitis-associated neoplasias. Gastroenterology 132(4):1254–1260, Epub 2007/04/06

    Article  PubMed  CAS  Google Scholar 

  88. Moriyama T, Matsumoto T, Nakamura S, Jo Y, Mibu R, Yao T et al (2007) Hypermethylation of p14 (ARF) may be predictive of colitic cancer in patients with ulcerative colitis. Dis Colon Rectum 50(9):1384–1392, Epub 2007/08/01

    Article  PubMed  Google Scholar 

  89. Dhir M, Montgomery EA, Glockner SC, Schuebel KE, Hooker CM, Herman JG et al (2008) Epigenetic regulation of WNT signaling pathway genes in inflammatory bowel disease (IBD) associated neoplasia. J Gastrointest Surg 12(10):1745–1753, Epub 2008/08/22

    Article  PubMed  Google Scholar 

  90. Edwards RA, Witherspoon M, Wang K, Afrasiabi K, Pham T, Birnbaumer L et al (2009) Epigenetic repression of DNA mismatch repair by inflammation and hypoxia in inflammatory bowel disease-associated colorectal cancer. Cancer Res 69(16):6423–6429, Epub 2009/07/30

    Article  PubMed  CAS  Google Scholar 

  91. Arasaradnam RP, Khoo K, Bradburn M, Mathers JC, Kelly SB (2010) DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with ulcerative colitis (UC). Epigenetics 5(5):422–426, Epub 2010/05/28

    Article  PubMed  CAS  Google Scholar 

  92. Kuester D, Guenther T, Biesold S, Hartmann A, Bataille F, Ruemmele P et al (2010) Aberrant methylation of DAPK in long-standing ulcerative colitis and ulcerative colitis-associated carcinoma. Pathol Res Pract 206(9):616–624, Epub 2010/07/16

    Article  PubMed  CAS  Google Scholar 

  93. Olaru AV, Selaru FM, Mori Y, Vazquez C, David S, Paun B et al (2011) Dynamic changes in the expression of MicroRNA-31 during inflammatory bowel disease-associated neoplastic transformation. Inflamm Bowel Dis 17(1):221–231, Epub 2010/09/18

    Article  PubMed  Google Scholar 

  94. Bakirtzi K, Hatziapostolou M, Karagiannides I, Polytarchou C, Jaeger S, Iliopoulos D et al (2011) Neurotensin signaling activates microRNAs-21 and -155 and Akt, promotes tumor growth in mice, and is increased in human colon tumors. Gastroenterology 141(5):1749.e1–1761.e1, Epub 2011/08/03

    Article  Google Scholar 

  95. Kanaan Z, Rai SN, Eichenberger MR, Barnes C, Dworkin AM, Weller C et al (2012) Differential microRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer. Hum Mutat 33(3):551–560, Epub 2012/01/14

    Article  PubMed  CAS  Google Scholar 

  96. Sawyers CL (2008) The cancer biomarker problem. Nature 452(7187):548–552, Epub 2008/04/04

    Article  PubMed  CAS  Google Scholar 

  97. Begley CG, Ellis LM (2012) Drug development: raise standards for preclinical cancer research. Nature 483(7391):531–533, Epub 2012/03/31

    Article  PubMed  CAS  Google Scholar 

  98. Zahm AM, Thayu M, Hand NJ, Horner A, Leonard MB, Friedman JR (2011) Circulating microRNA is a biomarker of pediatric Crohn disease. J Pediatr Gastroenterol Nutr 53(1):26–33, Epub 2011/05/07

    Article  PubMed  CAS  Google Scholar 

  99. Wu F, Guo NJ, Tian H, Marohn M, Gearhart S, Bayless TM et al (2011) Peripheral blood microRNAs distinguish active ulcerative colitis and Crohn’s disease. Inflamm Bowel Dis 17(1):241–250, Epub 2010/09/03

    Article  PubMed  Google Scholar 

  100. Paraskevi A, Theodoropoulos G, Papaconstantinou I, Mantzaris G, Nikiteas N, Gazouli M (2012) Circulating microRNA in inflammatory bowel disease. J Crohns Colitis 6(9):900–904, Epub 2012/03/06

    Article  PubMed  Google Scholar 

  101. Rakyan VK, Hildmann T, Novik KL, Lewin J, Tost J, Cox AV et al (2004) DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project. PLoS Biol 2(12):e405, Epub 2004/11/20

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Nationales Genomforschungsnetz (NGFN) grants by the BMBF, the EU grant gEUVADIS, the Deutsche Forschungsgemeinschaft (DFG) under contract numbers SFB877, RO2994/5-1, and the Cluster of Excellence Inflammation at Interfaces. SB was supported by a Royal Society Wolfson Research Merit Award (WM100023) and grants from the Wellcome Trust (084071) and EU-FP7 BLUEPRINT (282510). We apologize to those researchers whose important contributions to the field we were unable to include.

Author information

Authors and Affiliations

  1. Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105, Kiel, Germany

    Robert Häsler Ph.D., Stefan Schreiber M.D. & Philip Rosenstiel M.D.

  2. Department of General Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Stefan Schreiber M.D.

  3. UCL Cancer Institute, 72 Huntley Street, Paul O’Gorman Building, London, WC1E 6BT, UK

    Stephan Beck M.Sc., Ph.D.

Authors
  1. Robert Häsler Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stefan Schreiber M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephan Beck M.Sc., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philip Rosenstiel M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Stephan Beck M.Sc., Ph.D. or Philip Rosenstiel M.D. .

Editor information

Editors and Affiliations

  1. Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden

    Mauro D'Amato

  2. Research Center, Montreal Heart Institute, Montreal, Québec, Canada

    John D Rioux

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Häsler, R., Schreiber, S., Beck, S., Rosenstiel, P. (2013). Epigenetics of Inflammatory Bowel Disease. In: D'Amato, M., Rioux, J. (eds) Molecular Genetics of Inflammatory Bowel Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8256-7_9

Download citation

Publish with us

Policies and ethics

Search

Navigation