Exercise and inflammation-related epigenetic modifications: Focus on DNA methylation

Exercise Immunology Review

Volumn 21, Issue , 2015, Pages 26-41

  Horsburgh, Steven ^a   Robson Ansley, Paula ^a,b   Adams, Rozanne ^b   Smith, Carine ^b  

^a NORTHUMBRIA UNIVERSITY   (United Kingdom)

^b STELLENBOSCH UNIVERSITY   (South Africa)

Author keywords

DNA methyltransferase; Glucocorticoid; Nlrp3; Physical activity; Stress

Indexed keywords

CRYOPYRIN; DNA; GLUCOCORTICOID; INFLAMMASOME; INTERLEUKIN 1BETA; METHYL CPG BINDING PROTEIN; CARRIER PROTEIN; CIAS1 PROTEIN, MOUSE; CYTOKINE; DNA (CYTOSINE 5) METHYLTRANSFERASE; DNA BINDING PROTEIN; LIPOPOLYSACCHARIDE; METHYL-CPG DNA DEMETHYLASE; NLRP3 PROTEIN, HUMAN; O DEMETHYLASE;

DISEASE ASSOCIATION; DNA METHYLATION; DNA MODIFICATION; EPIGENOME; EXERCISE; GENOME; GENOME ANALYSIS; INFLAMMATION; INNATE IMMUNITY; MOLECULAR DYNAMICS; PHYSICAL ACTIVITY; PROTEIN DETERMINATION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; RISK ASSESSMENT; RISK FACTOR; ANIMAL; ATHLETE; COMPLICATION; CPG ISLAND; DIABETES MELLITUS, TYPE 2; DISEASE MODEL; DISEASE PREDISPOSITION; FORECASTING; GENETIC EPIGENESIS; GENETICS; HUMAN; IMMUNOLOGY; KINESIOTHERAPY; MATERNAL BEHAVIOR; MENTAL STRESS; METABOLISM; MOLECULARLY TARGETED THERAPY; NEOPLASMS; NEWBORN; OBESITY; PATHOPHYSIOLOGY; PHYSIOLOGY; RODENT;

ANIMALS; ANIMALS, NEWBORN; ATHLETES; CARRIER PROTEINS; CPG ISLANDS; CYTOKINES; DIABETES MELLITUS, TYPE 2; DISEASE MODELS, ANIMAL; DISEASE SUSCEPTIBILITY; DNA METHYLATION; DNA-BINDING PROTEINS; DNA-CYTOSINE METHYLASES; EPIGENESIS, GENETIC; EXERCISE; EXERCISE THERAPY; FORECASTING; GLUCOCORTICOIDS; HUMANS; INFLAMMASOMES; INFLAMMATION; LIPOPOLYSACCHARIDES; MATERNAL BEHAVIOR; MOLECULAR TARGETED THERAPY; NEOPLASMS; OBESITY; OXIDOREDUCTASES, O-DEMETHYLATING; RODENTIA; STRESS, PSYCHOLOGICAL;

EID: 84928696516     PISSN: 10775552     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (105)

1. Acharyya S, Sharma SM, Cheng AS, Ladner KJ, He W, Kline W, Wang H, Ostrowski MC, Huang TH, and Guttridge DC. TNF inhibits Notch-1 in skeletal muscle cells by Ezh2 and DNA methylation mediated repression: implications in duchenne muscular dystrophy. PLoS One 5:e12479, 2010.
2. Agrawal A, Tay J, Yang GE, Agrawal S, and Gupta S. Ageassociated epigenetic modifications in human DNA increase its immunogenicity. Aging (Albany NY) 2:93-100, 2010.
3. Alcocer-Gomez E, de Miguel M, Casas-Barquero N, Nunez-Vasco J, Sanchez-Alcazar JA, Fernandez-Rodriguez A, and Cordero MD. NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder. Brain Behav Immun 36:111-117, 2014.
4. Atreya R, and Neurath MF. Involvement of IL-6 in the pathogenesis of inflammatory bowel disease and colon cancer. Clin Rev Allergy Immunol 28:187-196, 2005.
5. Auclair G, and Weber M. Mechanisms of DNA methylation and demethylation in mammals. Biochimie 94:2202-2211, 2012.
6. Barrès R, Osler ME, Yan J, Rune A, Fritz T, Caidahl K, Krook A, and Zierath JR. Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density. Cell Metab 10:189-198, 2009.
7. Barrès R, Yan J, Egan B, Treebak JT, Rasmussen M, Fritz T, Caidahl K, Krook A, O'Gorman DJ, and Zierath JR. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab 15:405-411, 2012.
8. Bind MA, Baccarelli A, Zanobetti A, Tarantini L, Suh H, Vokonas P, and Schwartz J. Air pollution and markers of coagulation, inflammation, and endothelial function: associations and epigene-environment interactions in an elderly cohort. Epidemiology 23:332-340, 2012.
9. Braconi C, Huang N, and Patel T. MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor gene expression by interleukin-6 in human malignant cholangiocytes. Hepatology 51:881-890, 2010.
10. Bryan AD, Magnan RE, Hooper AE, Harlaar N, and Hutchison KE. Physical activity and differential methylation of breast cancer genes assayed from saliva: a preliminary investigation. Ann Behav Med 45:89-98, 2013.
11. Buck-Koehntop BA, and Defossez PA. On how mammalian transcription factors recognize methylated DNA. Epigenetics 8:131-137, 2013.
12. Champagne FA, Francis DD, Mar. A, and Meaney MJ. Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol Behav 79:359-371, 2003.
13. Chen T, Ueda Y, Dodge JE, Wang Z, and Li E. Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b. Mol Cell Biol 23:5594-5605, 2003.
14. Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, Carter C, Yu BP, and Leeuwenburgh C. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 8:18-30, 2009.
15. Clouaire T, and Stancheva I. Methyl-CpG binding proteins: specialized transcriptional repressors or structural components of chromatin? Cell Mol Life Sci 65:1509-1522, 2008.
16. Coyle YM, Xie XJ, Lewis CM, Bu D, Milchgrub S, and Euhus DM. Role of physical activity in modulating breast cancer risk as defined by APC and RASSF1A promoter hypermethylation in nonmalignant breast tissue. Cancer Epidemiol Biomarkers Prev 16:192-196, 2007.
17. Dabritz J, and Menheniott TR. Linking immunity, epigenetics, and cancer in inflammatory bowel disease. Inflamm Bowel Dis 20:1638-1654, 2014.
18. Ding Y, Li J, Liu S, Zhang L, Xiao H, Li J, Chen H, Petersen RB, Huang K, and Zheng L. DNA hypomethylation of inflammationassociated genes in adipose tissue of female mice after multigenerational high fat diet feeding. Int J Obes (Lond) 38:198-204, 2014.
19. Dragich J, Houwink-Manville I, and Schanen C. Rett syndrome: a surprising result of mutation in MECP2. Hum Mol Genet 9:2365-2375, 2000.
20. Duggan C, Xiao L, Terry MB, and McTiernan A. No effect of weight loss on LINE-1 methylation levels in peripheral blood leukocytes from postmenopausal overweight women. Obesity (Silver Spring) 22:2091-2096, 2014.
21. Edgett BA, Foster WS, Hankinson PB, Simpson CA, Little JP, Graham RB, and Gurd BJ. Dissociation of increases in PGC-1alpha and its regulators from exercise intensity and muscle activation following acute exercise. PLoS One 8:e71623, 2013.
22. Ehrlich M. The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease. Clin Immunol 109:17-28, 2003.
23. Enayati M, Solati J, Hosseini MH, Shahi HR, Saki G, and Salari AA. Maternal infection during late pregnancy increases anxiety- and depression-like behaviors with increasing age in male offspring. Brain Res Bull 87:295-302, 2012.
24. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S, Guler G, Morrison CD, Chan KK, Marcucci G, Calin GA, Huebner K, and Croce CM. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A 104:15805-15810, 2007.
25. Fischer CP. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev 12:6-33, 2006.
26. Fleshner M. Stress-evoked sterile inflammation, danger associated molecular patterns (DAMPs), microbial associated molecular patterns (MAMPs) and the inflammasome. Brain Behav Immun 27:1-7, 2013.
27. Foran E, Garrity-Park MM, Mureau C, Newell J, Smyrk TC, Limburg PJ, and Egan LJ. Upregulation of DNA methyltransferasemediated gene silencing, anchorage-independent growth, and migration of colon cancer cells by interleukin-6. Mol Cancer Res 8:471-481, 2010.
28. Francis D, Diorio J, Liu D, and Meaney MJ. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286:1155-1158, 1999.
29. Frank MG, Hershman SA, Weber MD, Watkins LR, and Maier SF. Chronic exposure to exogenous glucocorticoids primes microglia to pro-inflammatory stimuli and induces NLRP3 mRNA in the hippocampus. Psychoneuroendocrinology 40:191-200, 2014.
30. Fuke C, Shimabukuro M, Petronis A, Sugimoto J, Oda T, Miura K, Miyazaki T, Ogura C, Okazaki Y, and Jinno Y. Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann Hum Genet 68:196-204, 2004.
31. Fuks F, Hurd PJ, Wolf D, Nan X, Bird AP, and Kouzarides T. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem 278:4035-4040, 2003.
32. Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, Golic KG, Jacobsen SE, and Bestor TH. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311:395-398, 2006.
33. Guo W, Chung WY, Qian M, Pellegrini M, and Zhang MQ. Characterizing the strand-specific distribution of non-CpG methylation in human pluripotent cells. Nucleic Acids Res 42:3009-3016, 2014.
34. Gurvich N, Perna F, Farina A, Voza F, Menendez S, Hurwitz J, and Nimer SD. L3MBTL1 polycomb protein, a candidate tumor suppressor in del (20q12) myeloid disorders, is essential for genome stability. Proc Natl Acad Sci U S A 107:22552-22557, 2010.
35. Hara S, Takano T, Fujikawa T, Yamada M, Wakai T, Kono T, and Obata Y. Forced expression of DNA methyltransferases during oocyte growth accelerates the establishment of methylation imprints but not functional genomic imprinting. Hum Mol Genet 23:3853-3864, 2014.
36. Heid IM, Jackson AU, Randall JC, Winkler TW, Qi L, Steinthorsdottir V, Thorleifsson G, Zillikens MC, Speliotes EK, Magi R, Workalemahu T, White CC, Bouatia-Naji N, Harris TB, Berndt SI, Ingelsson E, Willer CJ, Weedon MN, Luan J, Vedantam S, Esko T, Kilpelainen TO, Kutalik Z, Li S, Monda KL, Dixon AL, Holmes CC, Kaplan LM, Liang L, Min JL, Moffatt MF, Molony C, Nicholson G, Schadt EE, Zondervan KT, Feitosa MF, Ferreira T, Lango Allen H, Weyant RJ, Wheeler E, Wood AR, Magic, Estrada K, Goddard ME, Lettre G, Mangino M, Nyholt DR, Purcell S, Smith AV, Visscher PM, Yang J, McCarroll SA, Nemesh J, Voight BF, Absher D, Amin N, Aspelund T, Coin L, Glazer NL, Hayward C, Heard-Costa NL, Hottenga JJ, Johansson A, Johnson T, Kaakinen M, Kapur K, Ketkar S, Knowles JW, Kraft P, Kraja AT, Lamina C, Leitzmann MF, McKnight B, Morris AP, Ong KK, Perry JR, Peters MJ, Polasek O, Prokopenko I, Rayner NW, Ripatti S, Rivadeneira F, Robertson NR, Sanna S, Sovio U, Surakka I, Teumer A, van Wingerden S, Vitart V, Zhao JH, Cavalcanti-Proenca C, Chines PS, Fisher E, Kulzer JR, Lecoeur C, Narisu N, Sandholt C, Scott LJ, Silander K, Stark K, Tammesoo ML, Teslovich TM, Timpson NJ, Watanabe RM, Welch R, Chasman DI, Cooper MN, Jansson JO, Kettunen J, Lawrence RW, Pellikka N, Perola M, Vandenput L, Alavere H, Almgren P, Atwood LD, Bennett AJ, Biffar R, Bonnycastle LL, Bornstein SR, Buchanan TA, Campbell H, Day IN, Dei M, Dorr M, Elliott P, Erdos MR, Eriksson JG, Freimer NB, Fu M, Gaget S, Geus EJ, Gjesing AP, Grallert H, Grassler J, Groves CJ, Guiducci C, Hartikainen AL, Hassanali N, Havulinna AS, Herzig KH, Hicks AA, Hui J, Igl W, Jousilahti P, Jula A, Kajantie E, Kinnunen L, Kolcic I, Koskinen S, Kovacs P, Kroemer HK, Krzelj V, Kuusisto J, Kvaloy K, Laitinen J, Lantieri O, Lathrop GM, Lokki ML, Luben RN, Ludwig B, McArdle WL, McCarthy A, Morken MA, Nelis M, Neville MJ, Pare G, Parker AN, Peden JF, Pichler I, Pietilainen KH, Platou CG, Pouta A, Ridderstrale M, Samani NJ, Saramies J, Sinisalo J, Smit JH, Strawbridge RJ, Stringham HM, Swift AJ, Teder-Laving M, Thomson B, Usala G, van Meurs JB, van Ommen GJ, Vatin V, Volpato CB, Wallaschofski H, Walters GB, Widen E, Wild SH, Willemsen G, Witte DR, Zgaga L, Zitting P, Beilby JP, James AL, Kahonen M, Lehtimaki T, Nieminen MS, Ohlsson C, Palmer LJ, Raitakari O, Ridker PM, Stumvoll M, Tonjes A, Viikari J, Balkau B, Ben-Shlomo Y, Bergman RN, Boeing H, Smith GD, Ebrahim S, Froguel P, Hansen T, Hengstenberg C, Hveem K, Isomaa B, Jorgensen T, Karpe F, Khaw KT, Laakso M, Lawlor DA, Marre M, Meitinger T, Metspalu A, Midthjell K, Pedersen O, Salomaa V, Schwarz PE, Tuomi T, Tuomilehto J, Valle TT, Wareham NJ, Arnold AM, Beckmann JS, Bergmann S, Boerwinkle E, Boomsma DI, Caulfield MJ, Collins FS, Eiriksdottir G, Gudnason V, Gyllensten U, Hamsten A, Hattersley AT, Hofman A, Hu FB, Illig T, Iribarren C, Jarvelin MR, Kao WH, Kaprio J, Launer LJ, Munroe PB, Oostra B, Penninx BW, Pramstaller PP, Psaty BM, Quertermous T, Rissanen A, Rudan I, Shuldiner AR, Soranzo N, Spector TD, Syvanen AC, Uda M, Uitterlinden A, Volzke H, Vollenweider P, Wilson JF, Witteman JC, Wright AF, Abecasis GR, Boehnke M, Borecki IB, Deloukas P, Frayling TM, Groop LC, Haritunians T, Hunter DJ, Kaplan RC, North KE, O'Connell JR, Peltonen L, Schlessinger D, Strachan DP, Hirschhorn JN, Assimes TL, Wichmann HE, Thorsteinsdottir U, van Duijn CM, Stefansson K, Cupples LA, Loos RJ, Barroso I, McCarthy MI, Fox CS, Mohlke KL, and Lindgren CM. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet 42:949-960, 2010.
37. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, Diez J, Sanchez-Mut JV, Setien F, Carmona FJ, Puca AA, Sayols S, Pujana MA, Serra-Musach J, Iglesias-Platas I, Formiga F, Fernandez AF, Fraga MF, Heath SC, Valencia A, Gut IG, Wang J, and Esteller M. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci U S A 109:10522-10527, 2012.
38. Hickie I, and Lloyd A. Are cytokines associated with neuropsychiatric syndromes in humans? Int J Immunopharmacol 17:677-683, 1995.
39. Hodge DR, Cho E, Copeland TD, Guszczynski T, Yang E, Seth AK, and Farrar WL. IL-6 enhances the nuclear translocation of DNA cytosine-5-methyltransferase 1 (DNMT1) via phosphorylation of the nuclear localization sequence by the AKT kinase. Cancer Genomics Proteomics 4:387-398, 2007.
40. Hodge DR, Li D, Qi SM, and Farrar WL. IL-6 induces expression of the Fli-1 proto-oncogene via STAT3. Biochem Biophys Res Commun 292:287-291, 2002.
41. Hodge DR, Peng B, Cherry JC, Hurt EM, Fox SD, Kelley JA, Munroe DJ, and Farrar WL. Interleukin 6 supports the maintenance of p53 tumor suppressor gene promoter methylation. Cancer Res 65:4673-4682, 2005.
42. Hodge DR, Xiao W, Clausen PA, Heidecker G, Szyf M, and Farrar WL. Interleukin-6 regulation of the human DNA methyltransferase (HDNMT) gene in human erythroleukemia cells. J Biol Chem 276:39508-39511, 2001.
43. Huang Y, Pastor WA, Shen Y, Tahiliani M, Liu DR, and Rao A. The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing. PLoS One 5:e8888, 2010.
44. Iwata M, Ota KT, and Duman RS. The inflammasome: pathways linking psychological stress, depression, and systemic illnesses. Brain Behav Immun 31:105-114, 2013.
45. Jacoby M, Gohrbandt S, Clausse V, Brons NH, and Muller CP. Interindividual variability and co-regulation of DNA methylation differ among blood cell populations. Epigenetics 7:1421-1434, 2012.
46. Kareta MS, Botello ZM, Ennis JJ, Chou C, and Chedin F. Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L. J Biol Chem 281:25893-25902, 2006.
47. Karouzakis E, Rengel Y, Jungel A, Kolling C, Gay RE, Michel BA, Tak PP, Gay S, Neidhart M, and Ospelt C. DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibroblasts. Genes Immun 12:643-652, 2011.
48. Keller P, Vollaard NB, Gustafsson T, Gallagher IJ, Sundberg CJ, Rankinen T, Britton SL, Bouchard C, Koch LG, and Timmons JA. A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype. J Appl Physiol (1985) 110:46-59, 2011.
49. Kitamura E, Igarashi J, Morohashi A, Hida N, Oinuma T, Nemoto N, Song F, Ghosh S, Held WA, Yoshida-Noro C, and Nagase H. Analysis of tissue-specific differentially methylated regions (TDMs) in humans. Genomics 89:326-337, 2007.
50. Kohli RM, and Zhang Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502:472-479, 2013.
51. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, Fitz Hugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, Le Vine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowski J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, and International Human Genome Sequencing C. Initial sequencing and analysis of the human genome. Nature 409:860-921, 2001.
52. Lei H, Oh SP, Okano M, Jutterman R, Goss KA, Jaenisch R, and Li E. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development 122, 3195-3205, 1996.
53. Levine S. Infantile experience and resistance to physiological stress. Science 126:405, 1957.
54. Li Y, Deuring J, Peppelenbosch MP, Kuipers EJ, de Haar C, and van der Woude CJ. IL-6-induced DNMT1 activity mediates SOCS3 promoter hypermethylation in ulcerative colitisrelated colorectal cancer. Carcinogenesis 33:1889-1896, 2012.
55. Liu CC, Lin JH, Hsu TW, Su K, Li AF, Hsu HS, and Hung SC. IL-6 enriched lung cancer stem-like cell population by inhibition of cell cycle regulators via DNMT1 upregulation. Int J Cancer 2014.
56. Lund EK, Belshaw NJ, Elliott GO, and Johnson IT. Recent advances in understanding the role of diet and obesity in the development of colorectal cancer. Proc Nutr Soc 70:194-204, 2011.
57. Luttropp K, Nordfors L, Ekstrom TJ, and Lind L. Physical activity is associated with decreased global DNA methylation in Swedish older individuals. Scand J Clin Lab Invest 73:184-185, 2013.
58. Mack GS. To selectivity and beyond. Nat Biotechnol 28:1259-1266, 2010.
59. Maslanik T, Mahaffey L, Tannura K, Beninson L, Greenwood BN, and Fleshner M. The inflammasome and danger associated molecular patterns (DAMPs) are implicated in cytokine and chemokine responses following stressor exposure. Brain Behav Immun 28:54-62, 2013.
60. McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med 363:2339-2350, 2010.
61. McGee SL, Sparling D, Olson AL, and Hargreaves M. Exercise increases MEF2- and GEF DNA-binding activity in human skeletal muscle. FASEB J 20:348-349, 2006.
62. Miller GE, and Chen E. Harsh family climate in early life presages the emergence of a proinflammatory phenotype in adolescence. Psychol Sci 21:848-856, 2010.
63. Mohammed AH, Henriksson BG, Soderstrom S, Ebendal T, Olsson T, and Seckl JR. Environmental influences on the central nervous system and their implications for the aging rat. Behav Brain Res 57:183-191, 1993.
64. Nakajima K, Takeoka M, Mori M, Hashimoto S, Sakurai A, Nose H, Higuchi K, Itano N, Shiohara M, Oh T, and Taniguchi S. Exercise effects on methylation of ASC gene. Int J Sports Med 31:671-675, 2010.
65. Nakano K, Boyle DL, and Firestein GS. Regulation of DNA methylation in rheumatoid arthritis synoviocytes. J Immunol 190:1297-1303, 2013.
66. Nakano K, Whitaker JW, Boyle DL, Wang W, and Firestein GS. DNA methylome signature in rheumatoid arthritis. Ann Rheum Dis 72:110-117, 2013.
67. Ng EK, Tsang WP, Ng SS, Jin HC, Yu J, Li JJ, Rocken C, Ebert MP, Kwok TT, and Sung JJ. MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer. Br J Cancer 101:699-706, 2009.
68. Nile CJ, Read RC, Akil M, Duff GW, and Wilson AG. Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis. Arthritis Rheum 58:2686-2693, 2008.
69. Nitert MD, Dayeh T, Volkov P, Elgzyri T, Hall E, Nilsson E, Yang BT, Lang S, Parikh H, Wessman Y, Weishaupt H, Attema J, Abels M, Wierup N, Almgren P, Jansson PA, Rünn T, Hansson O, Eriksson KF, Groop L, and Ling C. Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes. Diabetes 61:3322-3332, 2012.
70. Noll G. Pathogenesis of atherosclerosis: a possible relation to infection. Atherosclerosis 140 Suppl 1:S3-9, 1998.
71. Ntanasis-Stathopoulos J, Tzanninis JG, Philippou A, and Koutsilieris M. Epigenetic regulation on gene expression induced by physical exercise. J Musculoskelet Neuronal Interact 13:133-146, 2013.
72. Okano M, Bell DW, Haber DA, and Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247-257, 1999.
73. Olefsky JM, and Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72:219-246, 2010.
74. Olesen J, Kiilerich K, and Pilegaard H. PGC-1alpha-mediated adaptations in skeletal muscle. Pflugers Arch 460:153-162, 2010.
75. Pai AA, Bell JT, Marioni JC, Pritchard JK, and Gilad Y. A genome-wide study of DNA methylation patterns and gene expression levels in multiple human and chimpanzee tissues. PLoS Genet 7:e1001316, 2011.
76. Qin J, Van Buren D, Huang HS, Zhong L, Mostoslavsky R, Akbarian S, and Hock H. Chromatin protein L3MBTL1 is dispensable for development and tumor suppression in mice. J Biol Chem 285:27767-27775, 2010.
77. Reinius LE, Acevedo N, Joerink M, Pershagen G, Dahlen SE, Greco D, Soderhall C, Scheynius A, and Kere J. Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility. PLoS One 7:e41361, 2012.
78. Ren H, Collins V, Clarke SJ, Han JS, Lam P, Clay F, Williamson LM, and Andy Choo KH. Epigenetic changes in response to tai chi practice: a pilot investigation of DNA methylation marks. Evid Based Complement Alternat Med 2012:841810, 2012.
79. Robson-Ansley PJ, Saini A, Toms C, Ansley L, Walshe I, Nimmo MA, Curtin, JA. Dynamic changes in DNA methylation status in peripheral blood mononuclear cells following an acute bout of exercise: potential impact of exercise-induced elevations in interleukin-6 concentration. J Biol Regul Homeost Agents: in press, 2014.
80. Rönn T, Volkov P, Davegardh C, Dayeh T, Hall E, Olsson AH, Nilsson E, Tornberg A, Dekker Nitert M, Eriksson KF, Jones HA, Groop L, and Ling C. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet 9:e1003572, 2013.
81. Sakai Y, Suetake I, Shinozaki F, Yamashina S, and Tajima S. Co-expression of de novo DNA methyltransferases Dnmt3a2 and DnmtL in gonocytes of mouse embryos. Gene Expr Patterns 5:231-237, 2004.
82. Shaw B, Leung, WC, Tapp HS, Fitzpatrick AL, Saxton JM, and Belshaw, NJ. A change in physical activity level affects leukocyte DNA methylation of genes implicated in cardiovascular disease in the elderly. Proc Physiol Soc 31:C46, 2014.
83. Shuto T, Furuta T, Oba M, Xu H, Li JD, Cheung J, Gruenert DC, Uehara A, Suico MA, Okiyoneda T, and Kai H. 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 20:782-784, 2006.
84. Soares FH, and de Sousa MB. Different types of physical activity on inflammatory biomarkers in women with or without metabolic disorders: a systematic review. Women Health 53:298-316, 2013.
85. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, and Rao A. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930-935, 2009.
86. Takahashi K, Sugi Y, Hosono A, and Kaminogawa S. Epigenetic regulation of TLR4 gene expression in intestinal epithelial cells for the maintenance of intestinal homeostasis. J Immunol 183:6522-6529, 2009.
87. Travers ME, Mackay DJ, Dekker Nitert M, Morris AP, Lindgren CM, Berry A, Johnson PR, Hanley N, Groop LC, McCarthy MI, and Gloyn AL. Insights into the molecular mechanism for type 2 diabetes susceptibility at the KCNQ1 locus from temporal changes in imprinting status in human islets. Diabetes 62:987-992, 2013.
88. Van den Veyver IB, and Zoghbi HY. Mutations in the gene encoding methyl-CpG-binding protein 2 cause Rett syndrome. Brain Dev 23 Suppl 1:S147-151, 2001.
89. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, and Dixit VD. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17:179-188, 2011.
90. Waddington CH. Towards a Theoretical Biology, Vol. 1: Prolegomema. Edinburgh: Edinburgh University Press, 1968.
91. In: Jablonka E, and Lamb MJ. The changing concept of epigenetics. Annals of the New York Academy of Sciences 981:82-96, 2002.
92. Wade PA. Methyl CpG-binding proteins and transcriptional repression. Bioessays 23:1131-1137, 2001.
93. Walshe I, Robson-Ansley P, St Clair Gibson A, Lawrence C, Thompson KG, and Ansley L. The reliability of the IL-6, sIL-6R and sgp130 response to a preloaded time trial. Eur J Appl Physiol 110:619-625, 2010.
94. Weaver IC, Cervoni N, Champagne FA, D'Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, and Meaney MJ. Epigenetic programming by maternal behavior. Nat Neurosci 7:847-854, 2004.
95. Wehbe H, Henson R, Meng F, Mize-Berge J, and Patel T. Interleukin-6 contributes to growth in cholangiocarcinoma cells by aberrant promoter methylation and gene expression. Cancer Res 66:10517-10524, 2006.
96. Weiss H, Friedrich T, Hofhaus G, and Preis D. The respiratorychain NADH dehydrogenase (complex I) of mitochondria. Eur J Biochem 197:563-576, 1991.
97. White AJ, Sandler DP, Bolick SC, Xu Z, Taylor JA, and De Roo LA. Recreational and household physical activity at different time points and DNA global methylation. Eur J Cancer 49:2199-2206, 2013.
98. Wu HC, Delgado-Cruzata L, Flom JD, Kappil M, Ferris JS, Liao Y, Santella RM, and Terry MB. Global methylation profiles in DNA from different blood cell types. Epigenetics 6:76-85, 2011.
99. Wu C, and Morris JR. Genes, Genetics, and Epigenetics: A Correspondence. Science 293:1103-1105, 2001.
100. Yu M, Hon GC, Szulwach KE, Song CX, Zhang L, Kim A, Li X, Dai Q, Shen Y, Park B, Min JH, Jin P, Ren B, and He C. Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome. Cell 149:1368-1380, 2012.
101. Yuasa Y, Nagasaki H, Akiyama Y, Hashimoto Y, Takizawa T, Kojima K, Kawano T, Sugihara K, Imai K, and Nakachi K. DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients. Int J Cancer 124:2677-2682, 2009.
102. Zeng H, Irwin ML, Lu L, Risch H, Mayne S, Mu L, Deng Q, Scarampi L, Mitidieri M, Katsaros D, and Yu H. Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1. Breast Cancer Res Treat 133:127-135, 2012.
103. Zhang FF, Cardarelli R, Carroll J, Zhang S, Fulda KG, Gonzalez K, Vishwanatha JK, Morabia A, and Santella RM. Physical activity and global genomic DNA methylation in a cancer-free population. Epigenetics 6:293-299, 2011.
104. Zhang FF, Santella RM, Wolff M, Kappil MA, Markowitz SB, and Morabia A. White blood cell global methylation and IL-6 promoter methylation in association with diet and lifestyle risk factors in a cancer-free population. Epigenetics 7:606-614, 2012.
105. Zhang Q, Wang HY, Woetmann A, Raghunath PN, Odum N, and Wasik MA. STAT3 induces transcription of the DNA methyltransferase 1 gene (DNMT1) in malignant T lymphocytes. Blood 108:1058-1064, 2006.