Advertisement

Role of Epigenetics in Inflammation-Associated Diseases

  • Muthu K. Shanmugam
  • Gautam Sethi
Part of the Subcellular Biochemistry book series (SCBI, volume 61)

Abstract

There is considerable evidence suggesting that epigenetic mechanisms may mediate development of chronic inflammation by modulating the expression of pro-inflammatory cytokine TNF-α, interleukins, tumor suppressor genes, oncogenes and autocrine and paracrine activation of the transcription factor NF-κB. These molecules are constitutively produced by a variety of cells under chronic inflammatory conditions, which in turn leads to the development of major diseases such as autoimmune disorders, chronic obstructive pulmonary diseases, neurodegenerative diseases and cancer. Distinct or global changes in the epigenetic landscape are hallmarks of chronic inflammation driven diseases. Epigenetics include changes to distinct markers on the genome and associated cellular transcriptional machinery that are copied during cell division (mitosis and meiosis). These changes appear for a short span of time and they necessarily do not make permanent changes to the primary DNA sequence itself. However, the most frequently observed epigenetic changes include aberrant DNA methylation, and histone acetylation and deacetylation. In this chapter, we focus on pro-inflammatory molecules that are regulated by enzymes involved in epigenetic modifications such as arginine and lysine methyl transferases, DNA methyltransferase, histone acetyltransferases and histone deacetylases and their role in inflammation driven diseases. Agents that modulate or inhibit these epigenetic modifications, such as HAT or HDAC inhibitors have shown great potential in inhibiting the progression of these diseases. Given the plasticity of these epigenetic changes and their readiness to respond to intervention by small molecule inhibitors, there is a tremendous potential for the development of novel therapeutics that will serve as direct or adjuvant therapeutic compounds in the treatment of these diseases.

Keywords

Chronic Obstructive Pulmonary Disease Rheumatoid Arthritis Patient Histone Acetylation HDAC Inhibitor Epigenetic Modification 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Adenuga D, Yao H, March TH, Seagrave J, Rahman I (2009) Histone deacetylase 2 is phosphorylated, ubiquitinated, and degraded by cigarette smoke. Am J Respir Cell Mol Biol 40:464–473PubMedCrossRefGoogle Scholar
  2. Aggarwal B (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3:745–756PubMedCrossRefGoogle Scholar
  3. Aggarwal BB (2004) Nuclear factor-kappaB: the enemy within. Cancer Cell 6:203–208PubMedCrossRefGoogle Scholar
  4. Aggarwal BB, Gehlot P (2009) Inflammation and cancer: how friendly is the relationship for cancer patients? Curr Opin Pharmacol 9:351–369PubMedCrossRefGoogle Scholar
  5. Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G (2006) Inflammation and cancer: how hot is the link? Biochem Pharmacol 72:1605–1621PubMedCrossRefGoogle Scholar
  6. Agger K, Christensen J, Cloos PA, Helin K (2008) The emerging functions of histone demethylases. Curr Opin Genet Dev 18:159–168PubMedCrossRefGoogle Scholar
  7. Agrawal A, Tay J, Yang GE, Agrawal S, Gupta S (2010) Age-associated epigenetic modifications in human DNA increase its immunogenicity. Aging (Albany NY) 2:93–100Google Scholar
  8. Aguilar-Quesada R, Munoz-Gamez JA, Martin-Oliva D, Peralta-Leal A, Quiles-Perez R, Rodriguez-Vargas JM, Ruiz de Almodovar M, Conde C, Ruiz-Extremera A, Oliver FJ (2007) Modulation of transcription by PARP-1: consequences in carcinogenesis and inflammation. Curr Med Chem 14:1179–1187PubMedCrossRefGoogle Scholar
  9. Ahn KS, Aggarwal BB (2005) Transcription factor NF-kappaB: a sensor for smoke and stress signals. Ann N Y Acad Sci 1056:218–233PubMedCrossRefGoogle Scholar
  10. Ahn KS, Sethi G, Aggarwal BB (2007) Nuclear factor-kappa B: from clone to clinic. Curr Mol Med 7:619–637PubMedCrossRefGoogle Scholar
  11. Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP (1998) Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res 58:5489–5494PubMedGoogle Scholar
  12. Amur SG, Shanker G, Cochran JM, Ved HS, Pieringer RA (1986) Correlation between inhibition of myelin basic protein (arginine) methyltransferase by sinefungin and lack of compact myelin formation in cultures of cerebral cells from embryonic mice. J Neurosci Res 16:367–376PubMedCrossRefGoogle Scholar
  13. Anest V, Hanson JL, Cogswell PC, Steinbrecher KA, Strahl BD, Baldwin AS (2003) A nucleosomal function for IkappaB kinase-alpha in NF-kappaB-dependent gene expression. Nature 423:659–663PubMedCrossRefGoogle Scholar
  14. Aniello F, Colella G, Muscariello G, Lanza A, Ferrara D, Branno M, Minucci S (2006) Expression of four histone lysine-methyltransferases in parotid gland tumors. Anticancer Res 26:2063–2067PubMedGoogle Scholar
  15. Arif M, Pradhan SK, Thanuja GR, Vedamurthy BM, Agrawal S, Dasgupta D, Kundu TK (2009) Mechanism of p300 specific histone acetyltransferase inhibition by small molecules. J Med Chem 52:267–277PubMedCrossRefGoogle Scholar
  16. Arif M, Vedamurthy BM, Choudhari R, Ostwal YB, Mantelingu K, Kodaganur GS, Kundu TK (2010) Nitric oxide-mediated histone hyperacetylation in oral cancer: target for a water-soluble HAT inhibitor, CTK7A. Chem Biol 17:903–913PubMedCrossRefGoogle Scholar
  17. Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281:1305–1308PubMedCrossRefGoogle Scholar
  18. Bachmann IM, Halvorsen OJ, Collett K, Stefansson IM, Straume O, Haukaas SA, Salvesen HB, Otte AP, Akslen LA (2006) EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol 24:268–273PubMedCrossRefGoogle Scholar
  19. Baguet A, Bix M (2004) Chromatin landscape dynamics of the Il4-Il13 locus during T helper 1 and 2 development. Proc Natl Acad Sci U S A 101:11410–11415PubMedCrossRefGoogle Scholar
  20. Balasubramanyam K, Swaminathan V, Ranganathan A, Kundu TK (2003) Small molecule modulators of histone acetyltransferase p300. J Biol Chem 278:19134–19140PubMedCrossRefGoogle Scholar
  21. Balasubramanyam K, Altaf M, Varier RA, Swaminathan V, Ravindran A, Sadhale PP, Kundu TK (2004a) Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J Biol Chem 279:33716–33726PubMedCrossRefGoogle Scholar
  22. Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U, Kundu TK (2004b) Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem 279:51163–51171PubMedCrossRefGoogle Scholar
  23. Balkwill F (2009) Tumour necrosis factor and cancer. Nat Rev Cancer 9:361–371PubMedCrossRefGoogle Scholar
  24. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545PubMedCrossRefGoogle Scholar
  25. Barnes PJ (2009a) Role of HDAC2 in the pathophysiology of COPD. Annu Rev Physiol 71:451–464PubMedCrossRefGoogle Scholar
  26. Barnes PJ (2009b) Targeting the epigenome in the treatment of asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc 6:693–696PubMedCrossRefGoogle Scholar
  27. Barres R, Osler ME, Yan J, Rune A, Fritz T, Caidahl K, Krook A, Zierath JR (2009) Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density. Cell Metab 10:189–198PubMedCrossRefGoogle Scholar
  28. Bayarsaihan D (2011) Epigenetic mechanisms in inflammation. J Dent Res 90:9–17PubMedCrossRefGoogle Scholar
  29. Belyaev ND, Nalivaeva NN, Makova NZ, Turner AJ (2009) Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease. EMBO Rep 10:94–100PubMedCrossRefGoogle Scholar
  30. Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447:407–412PubMedCrossRefGoogle Scholar
  31. Bettstetter M, Woenckhaus M, Wild PJ, Rummele P, Blaszyk H, Hartmann A, Hofstadter F, Dietmaier W (2005) Elevated nuclear maspin expression is associated with microsatellite instability and high tumour grade in colorectal cancer. J Pathol 205:606–614PubMedCrossRefGoogle Scholar
  32. Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21PubMedCrossRefGoogle Scholar
  33. Bird A (2007) Perceptions of epigenetics. Nature 447:396–398PubMedCrossRefGoogle Scholar
  34. Bolden JE, Peart MJ, Johnstone RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5:769–784PubMedCrossRefGoogle Scholar
  35. Borrello MG, Degl’Innocenti D, Pierotti MA (2008) Inflammation and cancer: the oncogene-driven connection. Cancer Lett 267:262–270PubMedCrossRefGoogle Scholar
  36. Bowman RV, Wright CM, Davidson MR, Francis SM, Yang IA, Fong KM (2009) Epigenomic targets for the treatment of respiratory disease. Expert Opin Ther Targets 13:625–640PubMedCrossRefGoogle Scholar
  37. Brasacchio D, Okabe J, Tikellis C, Balcerczyk A, George P, Baker EK, Calkin AC, Brownlee M, Cooper ME, El-Osta A (2009) Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail. Diabetes 58:1229–1236PubMedCrossRefGoogle Scholar
  38. Brigati C, Noonan DM, Albini A, Benelli R (2002) Tumors and inflammatory infiltrates: friends or foes? Clin Exp Metastasis 19:247–258PubMedCrossRefGoogle Scholar
  39. Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, Glockner S, Piantadosi S, Gabrielson E, Pridham G, Pelosky K, Belinsky SA, Yang SC, Baylin SB, Herman JG (2008) DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med 358:1118–1128PubMedCrossRefGoogle Scholar
  40. Bruniquel D, Schwartz RH (2003) Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat Immunol 4:235–240PubMedCrossRefGoogle Scholar
  41. Bryant RJ, Cross NA, Eaton CL, Hamdy FC, Cunliffe VT (2007) EZH2 promotes proliferation and invasiveness of prostate cancer cells. Prostate 67:547–556PubMedCrossRefGoogle Scholar
  42. Bulk E, Sargin B, Krug U, Hascher A, Jun Y, Knop M, Kerkhoff C, Gerke V, Liersch R, Mesters RM, Hotfilder M, Marra A, Koschmieder S, Dugas M, Berdel WE, Serve H, Muller-Tidow C (2009) S100A2 induces metastasis in non-small cell lung cancer. Clin Cancer Res 15:22–29PubMedCrossRefGoogle Scholar
  43. Camelo S, Iglesias AH, Hwang D, Due B, Ryu H, Smith K, Gray SG, Imitola J, Duran G, Assaf B, Langley B, Khoury SJ, Stephanopoulos G, De Girolami U, Ratan RR, Ferrante RJ, Dangond F (2005) Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis. J Neuroimmunol 164:10–21PubMedCrossRefGoogle Scholar
  44. Castellano S, Milite C, Ragno R, Simeoni S, Mai A, Limongelli V, Novellino E, Bauer I, Brosch G, Spannhoff A, Cheng D, Bedford MT, Sbardella G (2010) Design, synthesis and biological evaluation of carboxy analogues of arginine methyltransferase inhibitor 1 (AMI-1). ChemMedChem 5:398–414PubMedCrossRefGoogle Scholar
  45. Chang X, Yamada R, Suzuki A, Sawada T, Yoshino S, Tokuhiro S, Yamamoto K (2005) Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in synovial tissue of rheumatoid arthritis. Rheumatology (Oxford) 44:40–50CrossRefGoogle Scholar
  46. Chang B, Chen Y, Zhao Y, Bruick RK (2007) JMJD6 is a histone arginine demethylase. Science 318:444–447PubMedCrossRefGoogle Scholar
  47. Chang X, Zhao Y, Sun S, Zhang Y, Zhu Y (2009) The expression of PADI4 in synovium of rheumatoid arthritis. Rheumatol Int 29:1411–1416PubMedCrossRefGoogle Scholar
  48. Chen LF, Greene WC (2003) Regulation of distinct biological activities of the NF-kappaB transcription factor complex by acetylation. J Mol Med 81:549–557PubMedCrossRefGoogle Scholar
  49. Chen L, Fischle W, Verdin E, Greene WC (2001) Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science 293:1653–1657CrossRefGoogle Scholar
  50. Chen KL, Wang SS, Yang YY, Yuan RY, Chen RM, Hu CJ (2009) The epigenetic effects of amyloid-beta(1–40) on global DNA and neprilysin genes in murine cerebral endothelial cells. Biochem Biophys Res Commun 378:57–61PubMedCrossRefGoogle Scholar
  51. Cheng D, Yadav N, King RW, Swanson MS, Weinstein EJ, Bedford MT (2004) Small molecule regulators of protein arginine methyltransferases. J Biol Chem 279:23892–23899PubMedCrossRefGoogle Scholar
  52. Cheung N, Chan LC, Thompson A, Cleary ML, So CW (2007) Protein arginine-methyltransferase-dependent oncogenesis. Nat Cell Biol 9:1208–1215PubMedCrossRefGoogle Scholar
  53. Chevillard-Briet M, Trouche D, Vandel L (2002) Control of CBP co-activating activity by arginine methylation. EMBO J 21:5457–5466PubMedCrossRefGoogle Scholar
  54. Choi KC, Jung MG, Lee YH, Yoon JC, Kwon SH, Kang HB, Kim MJ, Cha JH, Kim YJ, Jun WJ, Lee JM, Yoon HG (2009) Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation. Cancer Res 69:583–592PubMedCrossRefGoogle Scholar
  55. Chung YL, Lee MY, Wang AJ, Yao LF (2003) A therapeutic strategy uses histone deacetylase inhibitors to modulate the expression of genes involved in the pathogenesis of rheumatoid arthritis. Mol Ther 8:707–717PubMedCrossRefGoogle Scholar
  56. Cloos PA, Christensen J, Agger K, Maiolica A, Rappsilber J, Antal T, Hansen KH, Helin K (2006) The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3. Nature 442:307–311PubMedCrossRefGoogle Scholar
  57. Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ (1996) Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 271:736–741PubMedCrossRefGoogle Scholar
  58. Collett K, Eide GE, Arnes J, Stefansson IM, Eide J, Braaten A, Aas T, Otte AP, Akslen LA (2006) Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer. Clin Cancer Res 12:1168–1174PubMedCrossRefGoogle Scholar
  59. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867PubMedCrossRefGoogle Scholar
  60. Covic M, Hassa PO, Saccani S, Buerki C, Meier NI, Lombardi C, Imhof R, Bedford MT, Natoli G, Hottiger MO (2005) Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-kappaB-dependent gene expression. EMBO J 24:85–96PubMedCrossRefGoogle Scholar
  61. Croce CM (2008) Oncogenes and cancer. N Engl J Med 358:502–511PubMedCrossRefGoogle Scholar
  62. Cuthbert GL, Daujat S, Snowden AW, Erdjument-Bromage H, Hagiwara T, Yamada M, Schneider R, Gregory PD, Tempst P, Bannister AJ, Kouzarides T (2004) Histone deimination antagonizes arginine methylation. Cell 118:545–553PubMedCrossRefGoogle Scholar
  63. Das PM, Singal R (2004) DNA methylation and cancer. J Clin Oncol 22:4632–4642PubMedCrossRefGoogle Scholar
  64. Dashwood RH, Myzak MC, Ho E (2006) Dietary HDAC inhibitors: time to rethink weak ligands in cancer chemoprevention? Carcinogenesis 27:344–349PubMedCrossRefGoogle Scholar
  65. Ding L, Erdmann C, Chinnaiyan AM, Merajver SD, Kleer CG (2006) Identification of EZH2 as a molecular marker for a precancerous state in morphologically normal breast tissues. Cancer Res 66:4095–4099PubMedCrossRefGoogle Scholar
  66. Dobrovic A, Simpfendorfer D (1997) Methylation of the BRCA1 gene in sporadic breast cancer. Cancer Res 57:3347–3350PubMedGoogle Scholar
  67. Dou Y, Milne TA, Ruthenburg AJ, Lee S, Lee JW, Verdine GL, Allis CD, Roeder RG (2006) Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol 13:713–719PubMedCrossRefGoogle Scholar
  68. Duncan HF, Smith AJ, Fleming GJ, Cooper PR (2011) HDACi: cellular effects, opportunities for restorative dentistry. J Dent Res 90:1377–1388PubMedCrossRefGoogle Scholar
  69. Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463PubMedCrossRefGoogle Scholar
  70. El Mezayen R, El Gazzar M, Myer R, High KP (2009) Aging-dependent upregulation of IL-23p19 gene expression in dendritic cells is associated with differential transcription factor binding and histone modifications. Aging Cell 8:553–565PubMedCrossRefGoogle Scholar
  71. Eliseeva ED, Valkov V, Jung M, Jung MO (2007) Characterization of novel inhibitors of histone acetyltransferases. Mol Cancer Ther 6:2391–2398PubMedCrossRefGoogle Scholar
  72. El-Osta A, Brasacchio D, Yao D, Pocai A, Jones PL, Roeder RG, Cooper ME, Brownlee M (2008) Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med 205:2409–2417PubMedCrossRefGoogle Scholar
  73. Ermann J, Fathman CG (2001) Autoimmune diseases: genes, bugs and failed regulation. Nat Immunol 2:759–761PubMedCrossRefGoogle Scholar
  74. Esteller M (2008) Epigenetics in cancer. N Engl J Med 358:1148–1159PubMedCrossRefGoogle Scholar
  75. Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature 447:433–440PubMedCrossRefGoogle Scholar
  76. Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4:143–153PubMedCrossRefGoogle Scholar
  77. Feldmann M, Maini RN (1999) The role of cytokines in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 38(Suppl 2):3–7Google Scholar
  78. Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361PubMedCrossRefGoogle Scholar
  79. Fleming JL, Huang TH, Toland AE (2008) The role of parental and grandparental epigenetic alterations in familial cancer risk. Cancer Res 68:9116–9121PubMedCrossRefGoogle Scholar
  80. Foster SL, Hargreaves DC, Medzhitov R (2007) Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447:972–978PubMedGoogle Scholar
  81. Frew AJ, Johnstone RW, Bolden JE (2009) Enhancing the apoptotic and therapeutic effects of HDAC inhibitors. Cancer Lett 280:125–133PubMedCrossRefGoogle Scholar
  82. Frietze S, Lupien M, Silver PA, Brown M (2008) CARM1 regulates estrogen-stimulated breast cancer growth through up-regulation of E2F1. Cancer Res 68:301–306PubMedCrossRefGoogle Scholar
  83. Futscher BW, Oshiro MM, Wozniak RJ, Holtan N, Hanigan CL, Duan H, Domann FE (2002) Role for DNA methylation in the control of cell type specific maspin expression. Nat Genet 31:175–179PubMedCrossRefGoogle Scholar
  84. Futscher BW, O’Meara MM, Kim CJ, Rennels MA, Lu D, Gruman LM, Seftor RE, Hendrix MJ, Domann FE (2004) Aberrant methylation of the maspin promoter is an early event in human breast cancer. Neoplasia 6:380–389PubMedCrossRefGoogle Scholar
  85. Goldstein AM (2004) Familial melanoma, pancreatic cancer and germline CDKN2A mutations. Hum Mutat 23:630PubMedCrossRefGoogle Scholar
  86. Gonzalez-Zulueta M, Bender CM, Yang AS, Nguyen T, Beart RW, Van Tornout JM, Jones PA (1995) Methylation of the 5′ CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res 55:4531–4535PubMedGoogle Scholar
  87. Grabiec AM, Tak PP, Reedquist KA (2008) Targeting histone deacetylase activity in rheumatoid arthritis and asthma as prototypes of inflammatory disease: should we keep our HATs on? Arthritis Res Ther 10:226PubMedCrossRefGoogle Scholar
  88. Graff JR, Herman JG, Lapidus RG, Chopra H, Xu R, Jarrard DF, Isaacs WB, Pitha PM, Davidson NE, Baylin SB (1995) E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res 55:5195–5199PubMedGoogle Scholar
  89. Greiner D, Bonaldi T, Eskeland R, Roemer E, Imhof A (2005) Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9. Nat Chem Biol 1:143–145PubMedCrossRefGoogle Scholar
  90. Gridelli C, Rossi A, Maione P (2008) The potential role of histone deacetylase inhibitors in the treatment of non-small-cell lung cancer. Crit Rev Oncol Hematol 68:29–36PubMedCrossRefGoogle Scholar
  91. Grivennikov SI, Karin M (2010) Inflammation and oncogenesis: a vicious connection. Curr Opin Genet Dev 20:65–71PubMedCrossRefGoogle Scholar
  92. Gronbaek K, de Nully BP, Moller MB, Nedergaard T, Ralfkiaer E, Moller P, Zeuthen J, Guldberg P (2000) Concurrent disruption of p16INK4a and the ARF-p53 pathway predicts poor prognosis in aggressive non-Hodgkin’s lymphoma. Leukemia 14:1727–1735PubMedCrossRefGoogle Scholar
  93. Gronbaek K, Hother C, Jones PA (2007) Epigenetic changes in cancer. APMIS 115:1039–1059PubMedCrossRefGoogle Scholar
  94. Grugel S, Finkenzeller G, Weindel K, Barleon B, Marme D (1995) Both v-Ha-Ras and v-Raf stimulate expression of the vascular endothelial growth factor in NIH 3T3 cells. J Biol Chem 270:25915–25919PubMedCrossRefGoogle Scholar
  95. Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, Nieland TJ, Zhou Y, Wang X, Mazitschek R, Bradner JE, DePinho RA, Jaenisch R, Tsai LH (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459:55–60PubMedCrossRefGoogle Scholar
  96. Guenther MG, Jenner RG, Chevalier B, Nakamura T, Croce CM, Canaani E, Young RA (2005) Global and Hox-specific roles for the MLL1 methyltransferase. Proc Natl Acad Sci USA 102:8603–8608PubMedCrossRefGoogle Scholar
  97. Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y (2004) SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol 6:731–740PubMedCrossRefGoogle Scholar
  98. Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, Nakamura Y, Furukawa Y (2006) Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci 97:113–118PubMedCrossRefGoogle Scholar
  99. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70PubMedCrossRefGoogle Scholar
  100. Harris AL (2002) Hypoxia–a key regulatory factor in tumour growth. Nat Rev Cancer 2:38–47PubMedCrossRefGoogle Scholar
  101. Hassa PO, Buerki C, Lombardi C, Imhof R, Hottiger MO (2003) Transcriptional coactivation of nuclear factor-kappaB-dependent gene expression by p300 is regulated by poly(ADP)-ribose polymerase-1. J Biol Chem 278:45145–45153PubMedCrossRefGoogle Scholar
  102. Hassa PO, Haenni SS, Buerki C, Meier NI, Lane WS, Owen H, Gersbach M, Imhof R, Hottiger MO (2005) Acetylation of poly(ADP-ribose) polymerase-1 by p300/CREB-binding protein regulates coactivation of NF-kappaB-dependent transcription. J Biol Chem 280:40450–40464PubMedCrossRefGoogle Scholar
  103. Hauke J, Riessland M, Lunke S, Eyupoglu IY, Blumcke I, El-Osta A, Wirth B, Hahnen E (2009) Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition. Hum Mol Genet 18:304–317PubMedCrossRefGoogle Scholar
  104. Hayakawa J, Mittal S, Wang Y, Korkmaz KS, Adamson E, English C, Ohmichi M, McClelland M, Mercola D (2004) Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress. Mol Cell 16:521–535PubMedCrossRefGoogle Scholar
  105. Hayes MP, Freeman SL, Donnelly RP (1995) IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and MRNA stability. Cytokine 7:427–435PubMedCrossRefGoogle Scholar
  106. Heidland A, Klassen A, Rutkowski P, Bahner U (2006) The contribution of Rudolf Virchow to the concept of inflammation: what is still of importance? J Nephrol 19(Suppl 10):S102–S109PubMedGoogle Scholar
  107. Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S, Samid D, Duan DS, Gnarra JR, Linehan WM et al (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA 91:9700–9704PubMedCrossRefGoogle Scholar
  108. Hess JL (2004) Mechanisms of transformation by MLL. Crit Rev Eukaryot Gene Expr 14:235–254PubMedCrossRefGoogle Scholar
  109. Hirst M, Marra MA (2009) Epigenetics and human disease. Int J Biochem Cell Biol 41:136–146PubMedCrossRefGoogle Scholar
  110. Hong H, Kao C, Jeng MH, Eble JN, Koch MO, Gardner TA, Zhang S, Li L, Pan CX, Hu Z, MacLennan GT, Cheng L (2004) Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status. Cancer 101:83–89PubMedCrossRefGoogle Scholar
  111. Hsieh CJ, Klump B, Holzmann K, Borchard F, Gregor M, Porschen R (1998) Hypermethylation of the p16INK4a promoter in colectomy specimens of patients with long-standing and extensive ulcerative colitis. Cancer Res 58:3942–3945PubMedGoogle Scholar
  112. Huang J, Sengupta R, Espejo AB, Lee MG, Dorsey JA, Richter M, Opravil S, Shiekhattar R, Bedford MT, Jenuwein T, Berger SL (2007) p53 is regulated by the lysine demethylase LSD1. Nature 449:105–108PubMedCrossRefGoogle Scholar
  113. Huber LC, Distler JH, Moritz F, Hemmatazad H, Hauser T, Michel BA, Gay RE, Matucci-Cerinic M, Gay S, Distler O, Jungel A (2007a) Trichostatin A prevents the accumulation of extracellular matrix in a mouse model of bleomycin-induced skin fibrosis. Arthritis Rheum 56:2755–2764PubMedCrossRefGoogle Scholar
  114. Huber LC, Stanczyk J, Jungel A, Gay S (2007b) Epigenetics in inflammatory rheumatic diseases. Arthritis Rheum 56:3523–3531PubMedCrossRefGoogle Scholar
  115. Huber K, Schemies J, Uciechowska U, Wagner JM, Rumpf T, Lewrick F, Suss R, Sippl W, Jung M, Bracher F (2010) Novel 3-arylideneindolin-2-ones as inhibitors of NAD+ -dependent histone deacetylases (sirtuins). J Med Chem 53:1383–1386PubMedCrossRefGoogle Scholar
  116. Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7:536–540PubMedCrossRefGoogle Scholar
  117. Issa JP, Ahuja N, Toyota M, Bronner MP, Brentnall TA (2001) Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res 61:3573–3577PubMedGoogle Scholar
  118. Issa JP, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S, Bayar E, Lyons J, Rosenfeld CS, Cortes J, Kantarjian HM (2004) Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103:1635–1640PubMedCrossRefGoogle Scholar
  119. Ito K, Barnes PJ, Adcock IM (2000) Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol 20:6891–6903PubMedCrossRefGoogle Scholar
  120. Ito K, Ito M, Elliott WM, Cosio B, Caramori G, Kon OM, Barczyk A, Hayashi S, Adcock IM, Hogg JC, Barnes PJ (2005) Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med 352:1967–1976PubMedCrossRefGoogle Scholar
  121. Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, Hosoki E, Kawashima-Morishima M, Lee HJ, Hama E, Sekine-Aizawa Y, Saido TC (2000) Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat Med 6:143–150PubMedCrossRefGoogle Scholar
  122. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33(Suppl):245–254PubMedCrossRefGoogle Scholar
  123. Jain RK, Safabakhsh N, Sckell A, Chen Y, Jiang P, Benjamin L, Yuan F, Keshet E (1998) Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: role of vascular endothelial growth factor. Proc Natl Acad Sci U S A 95:10820–10825PubMedCrossRefGoogle Scholar
  124. Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428PubMedCrossRefGoogle Scholar
  125. Jungel A, Baresova V, Ospelt C, Simmen BR, Michel BA, Gay RE, Gay S, Seemayer CA, Neidhart M (2006) Trichostatin A sensitises rheumatoid arthritis synovial fibroblasts for TRAIL-induced apoptosis. Ann Rheum Dis 65:910–912PubMedCrossRefGoogle Scholar
  126. Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, Jessup JM, Kolodner R (1997) Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 57:808–811PubMedGoogle Scholar
  127. Kang SH, Choi HH, Kim SG, Jong HS, Kim NK, Kim SJ, Bang YJ (2000) Transcriptional inactivation of the tissue inhibitor of metalloproteinase-3 gene by DNA hypermethylation of the 5′-CpG island in human gastric cancer cell lines. Int J Cancer 86:632–635PubMedCrossRefGoogle Scholar
  128. Kang GH, Lee S, Kim WH, Lee HW, Kim JC, Rhyu MG, Ro JY (2002) Epstein-barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma. Am J Pathol 160:787–794PubMedCrossRefGoogle Scholar
  129. Kang MY, Lee BB, Kim YH, Chang DK, Kyu Park S, Chun HK, Song SY, Park J, Kim DH (2007) Association of the SUV39H1 histone methyltransferase with the DNA methyltransferase 1 at mRNA expression level in primary colorectal cancer. Int J Cancer 121:2192–2197PubMedCrossRefGoogle Scholar
  130. Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441:431–436PubMedCrossRefGoogle Scholar
  131. Katzenellenbogen RA, Baylin SB, Herman JG (1999) Hypermethylation of the DAP-kinase CpG island is a common alteration in B-cell malignancies. Blood 93:4347–4353PubMedGoogle Scholar
  132. Kim HS, Kim EM, Kim NJ, Chang KA, Choi Y, Ahn KW, Lee JH, Kim S, Park CH, Suh YH (2004) Inhibition of histone deacetylation enhances the neurotoxicity induced by the C-terminal fragments of amyloid precursor protein. J Neurosci Res 75:117–124PubMedCrossRefGoogle Scholar
  133. Kondo Y, Shen L, Ahmed S, Boumber Y, Sekido Y, Haddad BR, Issa JP (2008) Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells. PLoS One 3:e2037PubMedCrossRefGoogle Scholar
  134. Koura AN, Liu W, Kitadai Y, Singh RK, Radinsky R, Ellis LM (1996) Regulation of vascular endothelial growth factor expression in human colon carcinoma cells by cell density. Cancer Res 56:3891–3894PubMedGoogle Scholar
  135. Kruys V, Thompson P, Beutler B (1993) Extinction of the tumor necrosis factor locus, and of genes encoding the lipopolysaccharide signaling pathway. J Exp Med 177:1383–1390PubMedCrossRefGoogle Scholar
  136. Kubicek S, O’Sullivan RJ, August EM, Hickey ER, Zhang Q, Teodoro ML, Rea S, Mechtler K, Kowalski JA, Homon CA, Kelly TA, Jenuwein T (2007) Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 25:473–481PubMedCrossRefGoogle Scholar
  137. Kuendgen A, Lubbert M (2008) Current status of epigenetic treatment in myelodysplastic syndromes. Ann Hematol 87:601–611PubMedCrossRefGoogle Scholar
  138. Laderoute KR, Alarcon RM, Brody MD, Calaoagan JM, Chen EY, Knapp AM, Yun Z, Denko NC, Giaccia AJ (2000) Opposing effects of hypoxia on expression of the angiogenic inhibitor thrombospondin 1 and the angiogenic inducer vascular endothelial growth factor. Clin Cancer Res 6:2941–2950PubMedGoogle Scholar
  139. Laird PW (2003) The power and the promise of DNA methylation markers. Nat Rev Cancer 3:253–266PubMedCrossRefGoogle Scholar
  140. Lal G, Zhang N, van der Touw W, Ding Y, Ju W, Bottinger EP, Reid SP, Levy DE, Bromberg JS (2009) Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J Immunol 182:259–273PubMedGoogle Scholar
  141. Lee JY, Sullivan KE (2001) Gamma interferon and lipopolysaccharide interact at the level of transcription to induce tumor necrosis factor alpha expression. Infect Immun 69:2847–2852PubMedCrossRefGoogle Scholar
  142. Lee JY, Kim NA, Sanford A, Sullivan KE (2003) Histone acetylation and chromatin conformation are regulated separately at the TNF-alpha promoter in monocytes and macrophages. J Leukoc Biol 73:862–871PubMedCrossRefGoogle Scholar
  143. Lee GR, Kim ST, Spilianakis CG, Fields PE, Flavell RA (2006) T helper cell differentiation: regulation by cis elements and epigenetics. Immunity 24:369–379PubMedCrossRefGoogle Scholar
  144. Lee MJ, Kim YS, Kummar S, Giaccone G, Trepel JB (2008) Histone deacetylase inhibitors in cancer therapy. Curr Opin Oncol 20:639–649PubMedCrossRefGoogle Scholar
  145. Lee G, Walser TC, Dubinett SM (2009) Chronic inflammation, chronic obstructive pulmonary disease, and lung cancer. Curr Opin Pulm Med 15:303–307PubMedCrossRefGoogle Scholar
  146. Li F, Sethi G (2010) Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. Biochim Biophys Acta 1805:167–180PubMedGoogle Scholar
  147. Li H, Rauch T, Chen ZX, Szabo PE, Riggs AD, Pfeifer GP (2006) The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem 281:19489–19500PubMedCrossRefGoogle Scholar
  148. Li Y, Reddy MA, Miao F, Shanmugam N, Yee JK, Hawkins D, Ren B, Natarajan R (2008) Role of the histone H3 lysine 4 methyltransferase, SET7/9, in the regulation of NF-kappaB-dependent inflammatory genes. Relevance to diabetes and inflammation. J Biol Chem 283:26771–26781PubMedCrossRefGoogle Scholar
  149. Lin HI, Chu SJ, Wang D, Feng NH (2004) Pharmacological modulation of TNF production in macrophages. J Microbiol Immunol Infect 37:8–15PubMedGoogle Scholar
  150. Lin HS, Hu CY, Chan HY, Liew YY, Huang HP, Lepescheux L, Bastianelli E, Baron R, Rawadi G, Clement-Lacroix P (2007) Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. Br J Pharmacol 150:862–872PubMedCrossRefGoogle Scholar
  151. Link A, Balaguer F, Goel A (2010) Cancer chemoprevention by dietary polyphenols: promising role for epigenetics. Biochem Pharmacol 80:1771–1792PubMedCrossRefGoogle Scholar
  152. Liu HL, Chen Y, Cui GH, Zhou JF (2005) Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation. Acta Pharmacol Sin 26:603–609PubMedCrossRefGoogle Scholar
  153. Luo D, Zhang B, Lv L, Xiang S, Liu Y, Ji J, Deng D (2006) Methylation of CpG islands of p16 associated with progression of primary gastric carcinomas. Lab Invest 86:591–598PubMedGoogle Scholar
  154. Mai A, Altucci L (2009) Epi-drugs to fight cancer: from chemistry to cancer treatment, the road ahead. Int J Biochem Cell Biol 41:199–213PubMedCrossRefGoogle Scholar
  155. Mai A, Cheng D, Bedford MT, Valente S, Nebbioso A, Perrone A, Brosch G, Sbardella G, De Bellis F, Miceli M, Altucci L (2008) epigenetic multiple ligands: mixed histone/protein methyltransferase, acetyltransferase, and class III deacetylase (sirtuin) inhibitors. J Med Chem 51:2279–2290PubMedCrossRefGoogle Scholar
  156. Majumder S, Liu Y, Ford OH 3rd, Mohler JL, Whang YE (2006) Involvement of arginine methyltransferase CARM1 in androgen receptor function and prostate cancer cell viability. Prostate 66:1292–1301PubMedCrossRefGoogle Scholar
  157. Mantovani A (2010) Molecular pathways linking inflammation and cancer. Curr Mol Med 10:369–373PubMedCrossRefGoogle Scholar
  158. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444PubMedCrossRefGoogle Scholar
  159. Marks PA, Xu WS (2009) Histone deacetylase inhibitors: potential in cancer therapy. J Cell Biochem 107:600–608PubMedCrossRefGoogle Scholar
  160. Mazure NM, Chen EY, Yeh P, Laderoute KR, Giaccia AJ (1996) Oncogenic transformation and hypoxia synergistically act to modulate vascular endothelial growth factor expression. Cancer Res 56:3436–3440PubMedGoogle Scholar
  161. McGarvey KM, Fahrner JA, Greene E, Martens J, Jenuwein T, Baylin SB (2006) Silenced tumor suppressor genes reactivated by DNA demethylation do not return to a fully euchromatic chromatin state. Cancer Res 66:3541–3549PubMedCrossRefGoogle Scholar
  162. McGuire W, Hill AV, Allsopp CE, Greenwood BM, Kwiatkowski D (1994) Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria. Nature 371:508–510PubMedCrossRefGoogle Scholar
  163. McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442PubMedCrossRefGoogle Scholar
  164. Medzhitov R, Horng T (2009) Transcriptional control of the inflammatory response. Nat Rev Immunol 9:692–703PubMedCrossRefGoogle Scholar
  165. Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB, Sidransky D (1995) 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med 1:686–692PubMedCrossRefGoogle Scholar
  166. Metzger E, Wissmann M, Yin N, Muller JM, Schneider R, Peters AH, Gunther T, Buettner R, Schule R (2005) LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 437:436–439PubMedGoogle Scholar
  167. Meyer N, Penn LZ (2008) Reflecting on 25 years with MYC. Nat Rev Cancer 8:976–990PubMedCrossRefGoogle Scholar
  168. Meyer R, Wolf SS, Obendorf M (2007) PRMT2, a member of the protein arginine methyltransferase family, is a coactivator of the androgen receptor. J Steroid Biochem Mol Biol 107:1–14PubMedCrossRefGoogle Scholar
  169. Miao F, Gonzalo IG, Lanting L, Natarajan R (2004) In vivo chromatin remodeling events leading to inflammatory gene transcription under diabetic conditions. J Biol Chem 279:18091–18097PubMedCrossRefGoogle Scholar
  170. Miao F, Smith DD, Zhang L, Min A, Feng W, Natarajan R (2008) Lymphocytes from patients with type 1 diabetes display a distinct profile of chromatin histone H3 lysine 9 dimethylation: an epigenetic study in diabetes. Diabetes 57:3189–3198PubMedCrossRefGoogle Scholar
  171. Miranda TB, Cortez CC, Yoo CB, Liang G, Abe M, Kelly TK, Marquez VE, Jones PA (2009) DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther 8:1579–1588PubMedCrossRefGoogle Scholar
  172. Moscarello MA, Brady GW, Fein DB, Wood DD, Cruz TF (1986) The role of charge microheterogeneity of basic protein in the formation and maintenance of the multilayered structure of myelin: a possible role in multiple sclerosis. J Neurosci Res 15:87–99PubMedCrossRefGoogle Scholar
  173. Myzak MC, Karplus PA, Chung FL, Dashwood RH (2004) A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. Cancer Res 64:5767–5774PubMedCrossRefGoogle Scholar
  174. Myzak MC, Dashwood WM, Orner GA, Ho E, Dashwood RH (2006a) Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice. FASEB J 20:506–508PubMedGoogle Scholar
  175. Myzak MC, Hardin K, Wang R, Dashwood RH, Ho E (2006b) Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells. Carcinogenesis 27:811–819PubMedCrossRefGoogle Scholar
  176. Myzak MC, Tong P, Dashwood WM, Dashwood RH, Ho E (2007) Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp Biol Med (Maywood) 232:227–234Google Scholar
  177. Nasu Y, Nishida K, Miyazawa S, Komiyama T, Kadota Y, Abe N, Yoshida A, Hirohata S, Ohtsuka A, Ozaki T (2008) Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced arthritis mouse model. Osteoarthritis Cartilage 16:723–732PubMedCrossRefGoogle Scholar
  178. Neidhart M, Rethage J, Kuchen S, Kunzler P, Crowl RM, Billingham ME, Gay RE, Gay S (2000) Retrotransposable L1 elements expressed in rheumatoid arthritis synovial tissue: association with genomic DNA hypomethylation and influence on gene expression. Arthritis Rheum 43:2634–2647PubMedCrossRefGoogle Scholar
  179. Nicholas AP, Lubin FD, Hallett PJ, Vattem P, Ravenscroft P, Bezard E, Zhou S, Fox SH, Brotchie JM, Sweatt JD, Standaert DG (2008) Striatal histone modifications in models of levodopa-induced dyskinesia. J Neurochem 106:486–494PubMedCrossRefGoogle Scholar
  180. Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, Chandwani R, Marazzi I, Wilson P, Coste H, White J, Kirilovsky J, Rice CM, Lora JM, Prinjha RK, Lee K, Tarakhovsky A (2010) Suppression of inflammation by a synthetic histone mimic. Nature 468:1119–1123PubMedCrossRefGoogle Scholar
  181. Nile CJ, Read RC, Akil M, Duff GW, Wilson AG (2008) Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis. Arthritis Rheum 58:2686–2693PubMedCrossRefGoogle Scholar
  182. Nishida K, Komiyama T, Miyazawa S, Shen ZN, Furumatsu T, Doi H, Yoshida A, Yamana J, Yamamura M, Ninomiya Y, Inoue H, Asahara H (2004) Histone deacetylase inhibitor suppression of autoantibody-mediated arthritis in mice via regulation of p16INK4a and p21(WAF1/Cip1) expression. Arthritis Rheum 50:3365–3376PubMedCrossRefGoogle Scholar
  183. Ohtani-Fujita N, Fujita T, Aoike A, Osifchin NE, Robbins PD, Sakai T (1993) CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene. Oncogene 8:1063–1067PubMedGoogle Scholar
  184. Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM, Su L, Xu G, Zhang Y (2005) hDOT1L links histone methylation to leukemogenesis. Cell 121:167–178PubMedCrossRefGoogle Scholar
  185. Osawa T, Chong JM, Sudo M, Sakuma K, Uozaki H, Shibahara J, Nagai H, Funata N, Fukayama M (2002) Reduced expression and promoter methylation of p16 gene in Epstein-Barr virus-associated gastric carcinoma. Jpn J Cancer Res 93:1195–1200PubMedCrossRefGoogle Scholar
  186. Ospelt C, Gay S (2008) The role of resident synovial cells in destructive arthritis. Best Pract Res Clin Rheumatol 22:239–252PubMedCrossRefGoogle Scholar
  187. Otterson GA, Khleif SN, Chen W, Coxon AB, Kaye FJ (1995) CDKN2 gene silencing in lung cancer by DNA hypermethylation and kinetics of p16INK4 protein induction by 5-aza 2′deoxycytidine. Oncogene 11:1211–1216PubMedGoogle Scholar
  188. Pal S, Vishwanath SN, Erdjument-Bromage H, Tempst P, Sif S (2004) Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes. Mol Cell Biol 24:9630–9645PubMedCrossRefGoogle Scholar
  189. Pho L, Grossman D, Leachman SA (2006) Melanoma genetics: a review of genetic factors and clinical phenotypes in familial melanoma. Curr Opin Oncol 18:173–179PubMedCrossRefGoogle Scholar
  190. Pledgie-Tracy A, Sobolewski MD, Davidson NE (2007) Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. Mol Cancer Ther 6:1013–1021PubMedCrossRefGoogle Scholar
  191. Pogribny IP, Tryndyak VP, Muskhelishvili L, Rusyn I, Ross SA (2007) Methyl deficiency, alterations in global histone modifications, and carcinogenesis. J Nutr 137:216S–222SPubMedGoogle Scholar
  192. Portela A, Esteller M (2010) Epigenetic modifications and human disease. Nat Biotechnol 28:1057–1068PubMedCrossRefGoogle Scholar
  193. Ragno R, Simeoni S, Castellano S, Vicidomini C, Mai A, Caroli A, Tramontano A, Bonaccini C, Trojer P, Bauer I, Brosch G, Sbardella G (2007) Small molecule inhibitors of histone arginine methyltransferases: homology modeling, molecular docking, binding mode analysis, and biological evaluations. J Med Chem 50:1241–1253PubMedCrossRefGoogle Scholar
  194. Rak J, Mitsuhashi Y, Bayko L, Filmus J, Shirasawa S, Sasazuki T, Kerbel RS (1995) Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res 55:4575–4580PubMedGoogle Scholar
  195. Rak J, Mitsuhashi Y, Sheehan C, Tamir A, Viloria-Petit A, Filmus J, Mansour SJ, Ahn NG, Kerbel RS (2000a) Oncogenes and tumor angiogenesis: differential modes of vascular endothelial growth factor up-regulation in ras-transformed epithelial cells and fibroblasts. Cancer Res 60:490–498PubMedGoogle Scholar
  196. Rak J, Yu JL, Klement G, Kerbel RS (2000b) Oncogenes and angiogenesis: signaling three-dimensional tumor growth. J Investig Dermatol Symp Proc 5:24–33PubMedCrossRefGoogle Scholar
  197. Ramirez-Carrozzi VR, Nazarian AA, Li CC, Gore SL, Sridharan R, Imbalzano AN, Smale ST (2006) Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response. Genes Dev 20:282–296PubMedCrossRefGoogle Scholar
  198. Ravindra KC, Selvi BR, Arif M, Reddy BA, Thanuja GR, Agrawal S, Pradhan SK, Nagashayana N, Dasgupta D, Kundu TK (2009) Inhibition of lysine acetyltransferase KAT3B/p300 activity by a naturally occurring hydroxynaphthoquinone, plumbagin. J Biol Chem 284:24453–24464PubMedCrossRefGoogle Scholar
  199. Reiman JM, Kmieciak M, Manjili MH, Knutson KL (2007) Tumor immunoediting and immunosculpting pathways to cancer progression. Semin Cancer Biol 17:275–287PubMedCrossRefGoogle Scholar
  200. Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M (1990) Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 33:1665–1673PubMedCrossRefGoogle Scholar
  201. Rosin MP, Anwar WA, Ward AJ (1994) Inflammation, chromosomal instability, and cancer: the schistosomiasis model. Cancer Res 54:1929s–1933sPubMedGoogle Scholar
  202. Saigo K, Yoshida K, Ikeda R, Sakamoto Y, Murakami Y, Urashima T, Asano T, Kenmochi T, Inoue I (2008) Integration of hepatitis B virus DNA into the myeloid/lymphoid or mixed-lineage leukemia (MLL4) gene and rearrangements of MLL4 in human hepatocellular carcinoma. Hum Mutat 29:703–708PubMedCrossRefGoogle Scholar
  203. Schottenfeld D, Beebe-Dimmer J (2006) Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin 56:69–83PubMedCrossRefGoogle Scholar
  204. Selvi BR, Batta K, Kishore AH, Mantelingu K, Varier RA, Balasubramanyam K, Pradhan SK, Dasgupta D, Sriram S, Agrawal S, Kundu TK (2010a) Identification of a novel inhibitor of coactivator-associated arginine methyltransferase 1 (CARM1)-mediated methylation of histone H3 Arg-17. J Biol Chem 285:7143–7152PubMedCrossRefGoogle Scholar
  205. Selvi BR, Mohankrishna DV, Ostwal YB, Kundu TK (2010b) Small molecule modulators of histone acetylation and methylation: a disease perspective. Biochim Biophys Acta 1799:810–828PubMedCrossRefGoogle Scholar
  206. Semenza GL (2000) Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol 35:71–103PubMedCrossRefGoogle Scholar
  207. Sen R, Baltimore D (1986, 2006) Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46(1986):705–716; Republished in 2006: J Immunol 177:7485–7496Google Scholar
  208. Sethi G, Tergaonkar V (2009) Potential pharmacological control of the NF-kappaB pathway. Trends Pharmacol Sci 30:313–321PubMedCrossRefGoogle Scholar
  209. Sethi G, Sung B, Aggarwal BB (2008) TNF: a master switch for inflammation to cancer. Front Biosci 13:5094–5107PubMedCrossRefGoogle Scholar
  210. Shchors K, Shchors E, Rostker F, Lawlor ER, Brown-Swigart L, Evan GI (2006) The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1beta. Genes Dev 20:2527–2538PubMedCrossRefGoogle Scholar
  211. Shen HM, Tergaonkar V (2009) NFkappaB signaling in carcinogenesis and as a potential molecular target for cancer therapy. Apoptosis 14:348–363PubMedCrossRefGoogle Scholar
  212. Sheta EA, Harding MA, Conaway MR, Theodorescu D (2000) Focal adhesion kinase, Rap1, and transcriptional induction of vascular endothelial growth factor. J Natl Cancer Inst 92:1065–1073PubMedCrossRefGoogle Scholar
  213. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941–953PubMedCrossRefGoogle Scholar
  214. Shi X, Kachirskaia I, Yamaguchi H, West LE, Wen H, Wang EW, Dutta S, Appella E, Gozani O (2007) Modulation of p53 function by SET8-mediated methylation at lysine 382. Mol Cell 27:636–646PubMedCrossRefGoogle Scholar
  215. Shuto T, Furuta T, Oba M, Xu H, Li JD, Cheung J, Gruenert DC, Uehara A, Suico MA, Okiyoneda T, Kai H (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 20:782–784PubMedGoogle Scholar
  216. Siegmund KD, Connor CM, Campan M, Long TI, Weisenberger DJ, Biniszkiewicz D, Jaenisch R, Laird PW, Akbarian S (2007) DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS One 2:e895PubMedCrossRefGoogle Scholar
  217. Smith JB, Haynes MK (2002) Rheumatoid arthritis–a molecular understanding. Ann Intern Med 136:908–922PubMedGoogle Scholar
  218. Spannhoff A, Machmur R, Heinke R, Trojer P, Bauer I, Brosch G, Schule R, Hanefeld W, Sippl W, Jung M (2007) A novel arginine methyltransferase inhibitor with cellular activity. Bioorg Med Chem Lett 17:4150–4153PubMedCrossRefGoogle Scholar
  219. Spannhoff A, Sippl W, Jung M (2009) Cancer treatment of the future: inhibitors of histone methyltransferases. Int J Biochem Cell Biol 41:4–11PubMedCrossRefGoogle Scholar
  220. Stirzaker C, Millar DS, Paul CL, Warnecke PM, Harrison J, Vincent PC, Frommer M, Clark SJ (1997) Extensive DNA methylation spanning the Rb promoter in retinoblastoma tumors. Cancer Res 57:2229–2237PubMedGoogle Scholar
  221. Sullivan KE, Reddy AB, Dietzmann K, Suriano AR, Kocieda VP, Stewart M, Bhatia M (2007) Epigenetic regulation of tumor necrosis factor alpha. Mol Cell Biol 27:5147–5160PubMedCrossRefGoogle Scholar
  222. Sun Y, Jiang X, Chen S, Price BD (2006) Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation. FEBS Lett 580:4353–4356PubMedCrossRefGoogle Scholar
  223. Sung B, Pandey MK, Ahn KS, Yi T, Chaturvedi MM, Liu M, Aggarwal BB (2008) Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of nuclear factor-kappaB-regulated gene products involved in cell survival, proliferation, invasion, and inflammation through inhibition of the inhibitory subunit of nuclear factor-kappaBalpha kinase, leading to potentiation of apoptosis. Blood 111:4880–4891PubMedCrossRefGoogle Scholar
  224. Surh YJ, Kundu JK, Na HK, Lee JS (2005) Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals. J Nutr 135:2993S–3001SPubMedGoogle Scholar
  225. Szlosarek P, Charles KA, Balkwill FR (2006) Tumour necrosis factor-alpha as a tumour promoter. Eur J Cancer 42:745–750PubMedCrossRefGoogle Scholar
  226. Takahashi K, Sugi Y, Hosono A, Kaminogawa S (2009) Epigenetic regulation of TLR4 gene expression in intestinal epithelial cells for the maintenance of intestinal homeostasis. J Immunol 183:6522–6529PubMedCrossRefGoogle Scholar
  227. Takami N, Osawa K, Miura Y, Komai K, Taniguchi M, Shiraishi M, Sato K, Iguchi T, Shiozawa K, Hashiramoto A, Shiozawa S (2006) Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis synovial cells. Arthritis Rheum 54:779–787PubMedCrossRefGoogle Scholar
  228. Takeda K, Akira S (2004) TLR signaling pathways. Semin Immunol 16:3–9PubMedCrossRefGoogle Scholar
  229. Tan J, Cang S, Ma Y, Petrillo RL, Liu D (2010) Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. J Hematol Oncol 3:5PubMedCrossRefGoogle Scholar
  230. Taylor CT (2008) Interdependent roles for hypoxia inducible factor and nuclear factor-kappaB in hypoxic inflammation. J Physiol 586:4055–4059PubMedCrossRefGoogle Scholar
  231. Tsai EY, Falvo JV, Tsytsykova AV, Barczak AK, Reimold AM, Glimcher LH, Fenton MJ, Gordon DC, Dunn IF, Goldfeld AE (2000) A lipopolysaccharide-specific enhancer complex involving Ets, Elk-1, Sp1, and CREB binding protein and p300 is recruited to the tumor necrosis factor alpha promoter in vivo. Mol Cell Biol 20:6084–6094PubMedCrossRefGoogle Scholar
  232. Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439:811–816PubMedCrossRefGoogle Scholar
  233. Urdinguio RG, Sanchez-Mut JV, Esteller M (2009) Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol 8:1056–1072PubMedCrossRefGoogle Scholar
  234. Vaissiere T, Sawan C, Herceg Z (2008) Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res 659:40–48PubMedCrossRefGoogle Scholar
  235. Vallabhapurapu S, Karin M (2009) Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27:693–733PubMedCrossRefGoogle Scholar
  236. Vedel M, Lawrence F, Robert-Gero M, Lederer E (1978) The antifungal antibiotic sinefungin as a very active inhibitor of methyltransferases and of the transformation of chick embryo fibroblasts by Rous sarcoma virus. Biochem Biophys Res Commun 85:371–376PubMedCrossRefGoogle Scholar
  237. Verbiest V, Montaudon D, Tautu MT, Moukarzel J, Portail JP, Markovits J, Robert J, Ichas F, Pourquier P (2008) Protein arginine (N)-methyl transferase 7 (PRMT7) as a potential target for the sensitization of tumor cells to camptothecins. FEBS Lett 582:1483–1489PubMedCrossRefGoogle Scholar
  238. Villagra A, Sotomayor EM, Seto E (2010) Histone deacetylases and the immunological network: implications in cancer and inflammation. Oncogene 29:157–173PubMedCrossRefGoogle Scholar
  239. Villeneuve LM, Reddy MA, Lanting LL, Wang M, Meng L, Natarajan R (2008) Epigenetic histone H3 lysine 9 methylation in metabolic memory and inflammatory phenotype of vascular smooth muscle cells in diabetes. Proc Natl Acad Sci USA 105:9047–9052PubMedCrossRefGoogle Scholar
  240. Vossenaar ER, Radstake TR, van der Heijden A, van Mansum MA, Dieteren C, de Rooij DJ, Barrera P, Zendman AJ, van Venrooij WJ (2004) Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Ann Rheum Dis 63:373–381PubMedCrossRefGoogle Scholar
  241. Wagner JM, Hackanson B, Lubbert M, Jung M (2010) Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy. Clin Epigenet 1:117–136CrossRefGoogle Scholar
  242. Wang J, Lee JJ, Wang L, Liu DD, Lu C, Fan YH, Hong WK, Mao L (2004) Value of p16INK4a and RASSF1A promoter hypermethylation in prognosis of patients with resectable non-small cell lung cancer. Clin Cancer Res 10:6119–6125PubMedCrossRefGoogle Scholar
  243. Weinberg RA (1994) Oncogenes and tumor suppressor genes. CA Cancer J Clin 44:160–170PubMedCrossRefGoogle Scholar
  244. Wells AD (2009) New insights into the molecular basis of T cell anergy: anergy factors, avoidance sensors, and epigenetic imprinting. J Immunol 182:7331–7341PubMedCrossRefGoogle Scholar
  245. Wierda RJ, Geutskens SB, Jukema JW, Quax PH, van den Elsen PJ (2010) Epigenetics in atherosclerosis and inflammation. J Cell Mol Med 14:1225–1240PubMedCrossRefGoogle Scholar
  246. Wilson AG (2008) Epigenetic regulation of gene expression in the inflammatory response and relevance to common diseases. J Periodontol 79:1514–1519PubMedCrossRefGoogle Scholar
  247. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW (1997) Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA 94:3195–3199PubMedCrossRefGoogle Scholar
  248. Wissmann M, Yin N, Muller JM, Greschik H, Fodor BD, Jenuwein T, Vogler C, Schneider R, Gunther T, Buettner R, Metzger E, Schule R (2007) Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. Nat Cell Biol 9:347–353PubMedCrossRefGoogle Scholar
  249. Wolf JS, Chen Z, Dong G, Sunwoo JB, Bancroft CC, Capo DE, Yeh NT, Mukaida N, Van Waes C (2001) IL (interleukin)-1alpha promotes nuclear factor-kappaB and AP-1-induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas. Clin Cancer Res 7:1812–1820PubMedGoogle Scholar
  250. Wong ET, Tergaonkar V (2009) Roles of NF-kappaB in health and disease: mechanisms and therapeutic potential. Clin Sci (Lond) 116:451–465CrossRefGoogle Scholar
  251. Yamamoto Y, Verma UN, Prajapati S, Kwak YT, Gaynor RB (2003) Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression. Nature 423:655–659PubMedCrossRefGoogle Scholar
  252. Yang HJ, Liu VW, Wang Y, Tsang PC, Ngan HY (2006a) Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data. BMC Cancer 6:212PubMedCrossRefGoogle Scholar
  253. Yang SR, Chida AS, Bauter MR, Shafiq N, Seweryniak K, Maggirwar SB, Kilty I, Rahman I (2006b) Cigarette smoke induces proinflammatory cytokine release by activation of NF-kappaB and posttranslational modifications of histone deacetylase in macrophages. Am J Physiol Lung Cell Mol Physiol 291:L46–L57PubMedCrossRefGoogle Scholar
  254. Yang SR, Valvo S, Yao H, Kode A, Rajendrasozhan S, Edirisinghe I, Caito S, Adenuga D, Henry R, Fromm G, Maggirwar S, Li JD, Bulger M, Rahman I (2008) IKK alpha causes chromatin modification on pro-inflammatory genes by cigarette smoke in mouse lung. Am J Respir Cell Mol Biol 38:689–698PubMedCrossRefGoogle Scholar
  255. Yao H, Rahman I (2009) Current concepts on the role of inflammation in COPD and lung cancer. Curr Opin Pharmacol 9:375–383PubMedCrossRefGoogle Scholar
  256. Yoshiura K, Kanai Y, Ochiai A, Shimoyama Y, Sugimura T, Hirohashi S (1995) Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci USA 92:7416–7419PubMedCrossRefGoogle Scholar
  257. Zendman AJ, van Venrooij WJ, Pruijn GJ (2006) Use and significance of anti-CCP autoantibodies in rheumatoid arthritis. Rheumatology (Oxford) 45:20–25CrossRefGoogle Scholar
  258. Zhang Z, Zhang ZY, Fauser U, Schluesener HJ (2008) Valproic acid attenuates inflammation in experimental autoimmune neuritis. Cell Mol Life Sci 65:4055–4065PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Pharmacology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

Personalised recommendations