Epigenetics and environment: A complex relationship

Journal of Applied Physiology

Volumn 109, Issue 1, 2010, Pages 243-251

  Aguilera, Oscar ^a   Fernández, Agustín F ^b   Muñoz, Alberto ^a   Fraga, Mario F ^c  

^a UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

^b DEPARTAMENTO DE BIOQUÍMICA Y BIOLOGÍA MOLECULAR   (Spain)

^c CENTRO NACIONAL DE BIOTECNOLOGÍA   (Spain)

Author keywords

Chromatin; Epigenotype; Methylation

Indexed keywords

ANIMAL; DNA METHYLATION; ENVIRONMENT; FEMALE; GENETIC EPIGENESIS; HUMAN; MOUSE; RAT; REVIEW;

ANIMALS; DNA METHYLATION; ENVIRONMENT; EPIGENESIS, GENETIC; FEMALE; HUMANS; MICE; RATS;

EID: 77954324619     PISSN: 87507587     EISSN: 15221601     Source Type: Journal    
DOI: 10.1152/japplphysiol.00068.2010     Document Type: Review

References (115)

1. Agrelo R, Cheng WH, Setien F, Ropero S, Espada J, Fraga MF, Herranz M, Paz MF, Sanchez-Cespedes M, Artiga MJ, Guerrero D, Castells A, von Kobbe C, Bohr VA, Esteller M. Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc Natl. Acad. Sci USA 103: 8822-8827, 2006.
2. Agrelo R, Setien F, Espada J, Artiga MJ, Rodriguez M, Perez-Rosado A, Sanchez-Aguilera A, Fraga MF, Piris MA, Esteller M. Inactivation of the lamin A/C gene by CpG island promoter hypermethylation in hematologic malignancies, and its association with poor survival in nodal diffuse large B-cell lymphoma. J Clin Oncol 23: 3940-3947, 2005.
3. Allfrey VG, Faulkner R, Mirsky AE. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc Natl Acad Sci USA 51: 786-794, 1964.
4. Anway MD, Leathers C, Skinner MK. Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology 147: 5515-5523, 2006.
5. Avila MA, Garcia-Trevijano ER, Martinez-Chantar ML, Latasa MU, Perez-Mato I, Martinez-Cruz LA, del Pino MM, Corrales FJ, Mato JM. S-adenosylmethionine revisited: its essential role in the regulation of liver function. Alcohol 27: 163-167, 2002.
6. Bardag-Gorce F, French BA, Joyce M, Baires M, Montgomery RO, Li J, French S. Histone acetyltransferase p300 modulates gene expression in an epigenetic manner at high blood alcohol levels. Exp Mol Pathol 82: 197-202, 2007.
7. Beard C, Li E, Jaenisch R. Loss of methylation activates Xist in somatic but not in embryonic cells. Genes Dev 9: 2325-2334, 1995.
8. Belinsky SA, Palmisano WA, Gilliland FD, Crooks LA, Divine KK, Winters SA, Grimes MJ, Harms HJ, Tellez CS, Smith TM, Moots PP, Lechner JF, Stidley CA, Crowell RE. Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Res 62: 2370-2377, 2002.
9. Berdyshev GD, Korotaev GK, Boiarskikh GV, Vaniushin BF. [Nucleotide composition of DNA and RNA from somatic tissues of humpback and its changes during spawning], Biokhimiia 32: 988-993, 1967.
10. Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet 9: 2395-2402, 2000.
11. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev 16: 6-21, 2002.
12. Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, Yu W, Rongione MA, Ekstrom TJ, Harris TB, Launer LJ, Eiriksdottir G, Leppert MF, Sapienza C, Gudnason V, Feinberg AP. Intra-individual change over time in DNA methylation with familial clustering. JAMA 299: 2877-2883, 2008.
13. Bleich S, Lenz B, Ziegenbein M, Beutler S, Frieling H, Kornhuber J, Bonsch D. Epigenetic DNA hypermethylation of the HERP gene promoter induces down-regulation of its mRNA expression in patients with alcohol dependence. Alcohol Clin Exp Res 30: 587-591, 2006.
14. Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Monch K, Minucci S, Porse BT, Marine JC, Hansen KH, Helin K. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev 2.1: 525-530, 2007.
15. Brait M, Ford JG, Papaiahgari S, Garza MA, Lee JI, Loyo M, Maldonado L, Begum S, McCaffrey L, Howerton M, Sidransky D, Emerson MR, Ahmed S, Williams CD, Hoque MO. Association between lifestyle factors and CpG island methylation in a cancer-free population. Cancer Epidemiol Biomarkers Prev 18: 2984-2991, 2009.
16. Brosh RM Jr, Bohr VA. Roles of the Werner syndrome protein, in pathways required for maintenance of genome stability. Exp Gerontol 37 : 491-506, 2002.
17. Burdge GC, Slater-Jefferies J, Torrens C, Phillips ES, Hanson MA, Lillycrop KA. Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr 97: 435-439, 2007.
18. Calvanese V, Lara E, Kahn A, Fraga MF. The role of epigenetics in aging and age-related diseases. Ageing Res Rev 8: 268-276, 2009.
19. Casillas MA Jr, Lopatina N, Andrews LG, Tollefsbol TO. Transcriptional control of the DNA methyltransferases is altered in aging and neoplastically-transformed human fibroblasts. Mol Cell Biochem 252: 33-43, 2003.
20. Chen H, Ke Q, Kluz T, Yan Y, Costa M. Nickel ions increase histone H3 lysine 9 dimethylation and induce transgene silencing. Mol Cell Biol 26: 3728-3737, 2006.
21. Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Padbury JF, Bueno R, Sugarbaker DJ, Yeh RF, Wiencke JK, Kelsey KT. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 5: e1000602, 2009.
22. Chuang JC, Jones PA. Epigenetics and microRNAs. Pediatr Res 61: 24R-29R, 2007.
23. Dashwood RH, Ho E. Dietary histone deacetylase inhibitors: from cells to mice to man. Semin Cancer Biol 17: 363-369, 2007.
24. Doerfler W. Patterns of DNA methylation-evolutionary vestiges of foreign DNA inactivation as a host defense mechanism. A proposal. Biol Chem Hoppe Seyler 372: 557-564, 1991.
25. Epstein J, Williams JR, Little JB. Deficient DNA repair in human progeroid cells. Proc Natl Acad Sci U S A 70: 977-981, 1973.
26. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423: 293-298, 2003.
27. Esteller M. Epigenetics in cancer. N Engl J Med 358: 1148-1159, 2008.
28. Fang M, Chen D, Yang CS. Dietary polyphenols may affect DNA methylation. J Nutr 137: 223S-228S, 2007.
29. Fatemi M, Hermann A, Gowher H, Jeltsch A. Dnmt3a and Dnmtl functionally cooperate during de novo methylation of DNA. Eur J Biochem 269: 4981-4984, 2002.
30. Feinberg AP. Phenotypic plasticity and the epigenetics of human disease. Nature 447: 433-440, 2007.
31. Feinberg AP, Cui H, Ohlsson R. DNA methylation and genomic imprinting: insights from cancer into epigenetic mechanisms. Semin Cancer Biol 12: 389-398, 2002.
32. Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet 7: 21-33, 2006.
33. Fernandez-Ruiz J, Gomez M, Hernandez M, de Miguel R, Ramos JA. Cannabinoids and gene expression during brain development. Neurotox Res 6: 389-401, 2004.
34. Fleming JL, Huang TH, Toland AE. The role of parental and grandparental epigenetic alterations in familial cancer risk. Cancer Res 68: 9116-9121, 2008.
35. Fraga MF. Genetic and epigenetic regulation of aging. Curr Opin Immunol 21: 446-453, 2009.
36. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102: 10604-10609, 2005.
37. Fraga MF, Esteller M. Epigenetics and aging: the targets and the marks. Trends Genet 23: 413-418, 2007.
38. Gabory A, Attig L, Junien C. Sexual dimorphism in environmental epigenetic programming. Mol Cell Endocrinol 304: 8-18, 2009.
39. Gartner K. A third component causing random, variability beside environment and genotype. A reason for the limited success of a 30 year long effort to standardize laboratory animals? Lab Anim 24: 71-77, 1990.
40. Guarente L, Picard F. Calorie restriction-the SIR2 connection. Cell 120: 473-482, 2005.
41. Herman JG, Baylin SB. Gene silencing in cancer in association with, promoter hypermethylation. N Engl J Med 349: 2042-2054, 2003.
42. Holliday R. Epigenetics: a historical overview. Epigenetics 1: 76-80, 2006.
43. Holliday R. The inheritance of epigenetic defects. Science 238:163-170, 1987.
44. Issa JP. Age-related epigenetic changes and the immune system. Clin Immunol 109: 103-108, 2003.
45. Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, Cheng T, DePinho RA, Sharpless NE, Scadden DT. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443: 421-426, 2006.
46. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 3: 415-428, 2002.
47. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 293: 1068-1070, 2001.
48. Jung-Hynes B, Reiter RJ, Ahmad N. Sirtuins, melatonin and circadian rhythms: building a bridge between aging and cancer. J Pineal Res 48: 9-19, 2010.
49. Kaminsky ZA, Tang T, Wang SC, Ptak C, Oh GH, Wong AH, Feldcamp LA, Virtanen C, Halfvarson J, Tysk C, McRae AF, Visscher PM, Montgomery GW, Gottesman II, Martin NG, Petronis A. DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet 41: 240-245, 2009.
50. Ke Q, Davidson T, Chen H, Kluz T, Costa M. Alterations of histone modifications and transgene silencing by nickel chloride. Cardnogenesis 27: 1481-1488, 2006.
51. Keyes MK, Jang H, Mason JB, Liu Z, Crott JW, Smith DE, Friso S, Choi SW. Older age and dietary folate are determinants of genomic and p16-specific DNA methylation in mouse colon. J Nutr 137: 1713-1717, 2007.
52. Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S. Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases. EMBO J 21: 4183-4195, 2002.
53. Kim KC, Friso S, Choi SW. DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging. J Nutr Biochem 20: 917-926, 2009.
54. Kim WY, Sharpless NE. The regulation of INK4/ARF in cancer and aging. Cell 127: 265-275, 2006.
55. Kotsopoulos J, Sohn KJ, Kim YI. Postweaning dietary folate deficiency provided through childhood to puberty permanently increases genomic DNA methylation in adult rat liver. J Nutr 138: 703-709, 2008.
56. Kouzarides T. Chromatin modifications and their function. Cell 128: 693-705, 2007.
57. Kovalenko VM, Bagnyukova TV, Sergienko OV, Bondarenko LB, Shayakhmetova GM, Matvienko AV, Pogribny IP. Epigenetic changes in the rat livers induced by pyrazinamide treatment. Toxicol Appl Pharmacol 225: 293-299, 2007.
58. Launay JM, Del Pino M, Chironi G, Callebert J, Peoc'h K, Megnien JL, Mallet J, Simon A, Rendu F. Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation. PLoS One 4: e7959, 2009.
59. Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature 366: 362-365, 1993.
60. Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr 135: 1382-1386, 2005.
61. Lillycrop KA, Phillips ES, Torrens C, Hanson MA, Jackson AA, Burdge GC. Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring. Br J Nutr 100: 278-282, 2008.
62. Mafiini MV, Rubin BS, Sonnenschein C, Soto AM. Endocrine disrupters and reproductive health: the case of bisphenol-A. Mol Cell Endocrinol 254-255: 179-186, 2006.
63. Maze I, Covington HE, 3rd Dietz DM, LaPlant Q, Renthal W, Russo SJ, Mechanic M, Mouzon E, Neve RL, Haggarty SJ, Ren Y, Sampath SC, Hurd YL, Greengard P, Tarakhovsky A, Schaefer A, Nestler EJ. Essential role of the histone methyitransferase G9a in cocaine-induced plasticity. Science 327: 213-216, 2010.
64. Milagro FI, Campion J, Garcia-Diaz DF, Goyenechea E, Paternain L, Martinez JA. High fat diet-induced obesity modifies the methylation pattern of leptin promoter in rats. J Physiol Biochem 65: 1-9, 2009.
65. Morgan HD, Santos F, Green K, Dean W, Reik W. Epigenetic reprogramming in mammals. Hum Mol Genet 14, Spec No 1: R47-R58, 2005.
66. Morgan HD, Sutherland HG, Martin DI, Whitelaw E. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23: 314-318, 1999.
67. Myzak MC, Dashwood WM, Orner GA, Ho E, Dashwood RH. Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice. FASEB J 20: 506-508, 2006.
68. Nafee TM, Farrell WE, Carroll WD, Fryer AA, Ismail KM. Epigenetic control of fetal gene expression. BJOG 115: 158-168, 2008.
69. Novikova SI, He F, Bai J, Cutrufello NJ, Lidow MS, Undieh AS. Maternal cocaine administration in mice alters DNA methylation and gene expression in hippocampal neurons of neonatal and prepubertal offspring. PLoS One 3: e1919, 2008.
70. Oakes CC, Smiraglia DJ, Plass C, Trasler JM, Robaire B. Aging results in hypermethylation of ribosomal DNA in sperm, and liver of male rats. Proc Natl Acad Sci USA 100: 1775-1780, 2003.
71. Oliva J, Dedes J, Li J, French SW, Bardag-Gorce F. Epigenetics of proteasome inhibition in the liver of rats fed ethanol chronically. World J Gastroenterol 15: 705-712, 2009.
72. Opresko PL, Cheng WH, von Kobbe C, Harrigan JA, Bohr VA. Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis 24: 791-802, 2003.
73. Payer B, Lee JT. X chromosome dosage compensation: how mammals keep the balance. Annu Rev Genet 42: 733-772, 2008.
74. Plass C, Shibata H, Kalcheva I, Mullins L, Kotelevtseva N, Mullins J, Kato R, Sasaki H, Hirotsune S, Okazaki Y, Held WA, Hayashizaki Y, Chapman VM. Identification of Grfl on mouse chromosome 9 as an imprinted gene by RLGS-M. Nat Genet 14: 106-109, 1996.
75. Poulsen P, Esteller M, Vaag A, Fraga MF. The epigenetic basis of twin discordance in age-related diseases. Pediatr Res 61: 38R-42R, 2007.
76. Pruitt K, Zinn RL, Ohm JE, McGarvey KM, Kang SH, Watkins DN, Herman JG, Baylin SB. Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation. PLoS Genet 2: e40, 2006.
77. Rada-Iglesias A, Enroth S, Ameur A, Koch CM, Clelland GK, Respuela-Alonso P, Wilcox S, Dovey OM, Ellis PD, Langford CF, Dunham I, Komorowski J, Wadelius C. Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes. Genome Res 17: 708-719, 2007.
78. Rakyan VK, Beck S. Epigenetic variation and inheritance in mammals. Curr Opin Genet Dev 16: 573-577, 2006.
79. Romieu P, Host L, Gobaille S, Sandner G, Aunis D, Zwiller J. Histone deacetylase inhibitors decrease cocaine but not sucrose self-administration in rats. J Neurosci 28: 9342-9348, 2008.
80. Salnikow K, Costa M. Epigenetic mechanisms of nickel carcinogenesis. J Environ Pathol Toxicol. Oncol 19: 307-318, 2000.
81. Sarg B, Koutzamani E, Helliger W, Rundquist I, Lindner HH. Postsynthetic trimethylation of histone H4 at lysine 20 in mammalian tissues is associated with aging. J Biol Chem 277: 39195-39201, 2002.
82. Sasaki T, Maier B, Bartke A, Scrable H. Progressive loss of SIRT1 with cell cycle withdrawal. Aging Cell 5: 413-422, 2006.
83. Sato K, Fukata H, Kogo Y, Ohgane J, Shiota K, Mori C. Neonatal exposure to diethylstilbestrol alters expression of DNA methyltransferases and methylation of genomic DNA in the mouse uterus. Endocr J 56: 131-139, 2009.
84. Scaffidi P, Misteli T. Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat Cell Biol 10: 452-459, 2008.
85. Scaffidi P, Misteli T. Lamin A-dependent nuclear defects in human, aging. Science 312: 1059-1063, 2006.
86. Scaffidi P, Misteli T. Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med 11: 440-445, 2005.
87. Shiao YH, Crawford EB, Anderson LM, Patel P, Ko K. Allele-specific germ cell epimutation in the spacer promoter of the 45S ribosomal RNA gene after Cr(III) exposure. Toxicol, Appl Pharmacol, 205: 290-296, 2005.
88. Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, Eriksson M, Goldman AE, Khuon S, Collins FS, Jenuwein T, Goldman RD. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci USA 103: 8703-8708, 2006.
89. Simmons R. Developmental origins of adult metabolic disease: concepts and controversies. Trends Endocrinol Metab 16: 390-394, 2005.
90. Sinclair KD, Allegrucci C, Singh R, Gardner DS, Sebastian S, Bispham J, Thurston A, Huntley JF, Rees WD, Maloney CA, Lea RG, Craigon J, McEvoy TG, Young LE. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl. Acad Sci U S A 104: 19351-19356, 2007.
91. So K, Tamura G, Honda T, Homma N, Waki T, Togawa N, Nishizuka S, Motoyama T. Multiple tumor suppressor genes are increasingly methylated with, age in non-neoplastic gastric epithelia. Cancer Sci 97: 1155-1158, 2006.
92. Sommer M, Poliak N, Upadhyay S, Ratovitski E, Ndkin BD, Donehower LA, Sidransky D. DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. Cell Cycle 5: 2005-2011, 2006.
93. Takiguchi M, Achanzar WE, Qu W, Li G, Waalkes MP. Effects of cadmium, on DNA-(cytosine-5) methyitransferase activity and DNA methylation status during cadmium-induced cellular transformation. Exp Cell Res 286: 355-365, 2003.
94. Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, Slagboom PE, Heijmans BT. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet 18: 4046-4053, 2009.
95. Tremolizzo L, Carboni G, Ruzicka WB, Mitchell CP, Sugaya I, Tueting P, Sharma R, Grayson DR, Costa E, Guidotti A. An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability. Proc Natl Acad Sci USA 99: 17095-17100, 2002.
96. Tsygankov D, Liu Y, Sanoff HK, Sharpless NE, Elston TC. A quantitative model for age-dependent expression of the p16INK4a tumor suppressor. Proc Natl. Acad Sci USA 106: 16562-16567, 2009.
97. Umlauf D, Fraser P, Nagano T. The role of long non-coding RNAs in chromatin structure and gene regulation: variations on a theme. Biol Chem 389: 323-331, 2008.
98. Vanyushin BF, Nemirovsky LE, Klimenko VV, Vasiliev VK, Belozersky AN. The 5-methylcytosine in DNA of rats. Tissue and age specificity and the changes induced by hydrocortisone and other agents. Gerontologia 19: 138-152, 1973.
99. Vaquero A, Scher M, Lee D, Erdjument-Bromage H, Tempst P, Reinberg D. Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol Cell 16: 93-105, 2004.
100. Veurink M, Koster M, Berg LT. The history of DES, lessons to be learned. Pharm World Sci 27: 139-143, 2005.
101. Villar-Garea A, Esteller M. Histone deacetylase inhibitors: understanding a new wave of anticancer agents. Int J Cancer 112: 171-178, 2004.
102. Villar-Garea A, Fraga MF, Espada J, Esteller M. Procaine is a DNA-demethylating agent with growth-inhibitory effects in human, cancer cells. Cancer Res 63: 4984-4989, 2003.
103. Vogt G, Huber M, Thiemann M, van den Boogaart G, Schmitz OJ, Schubart CD. Production of different phenotypes from the same genotype in the same environment by developmental variation. J Exp Biol 211: 510-523, 2008.
104. Waddington CH. The epigenotype. Endeavour 1: 18-20, 1942.
105. Warri A, Saarinen NM, Makela S, Hilakivi-Clarke L. The role of early life genistein exposures in modifying breast cancer risk. Br J Cancer 98: 1485-1493, 2008.
106. Waterland RA. Assessing the effects of high methionine intake on DNA methylation. J Nutr 136: 1706S-1710S, 2006.
107. Waterland RA. Do maternal methyl supplements in mice affect DNA methylation of offspring? J Nutr 133: 238; author reply 239, 2003.
108. Waterland RA, Dolinoy DC, Lin JR, Smith CA, Shi X, Tahiliani KG. Maternal methyl supplements increase offspring DNA methylation at axin fused. Genesis 44: 401-406, 2006.
109. Waterland RA, Travisano M, Tahiliani KG, Rached MT, Mirza S. Methyl donor supplementation prevents transgenerational amplification of obesity. Int J Obes (Lond) 32: 1373-1379, 2008.
110. Whitelaw NC, Whitelaw E. How lifetimes shape epigenotype within and across generations. Hum Mol Genet 15, Spec No 2: R131-137, 2006.
111. Wilson VL, Jones PA. DNA methylation decreases in aging but not in immortal cells. Science 220: 1055-1057, 1983.
112. Wilson VL, Smith RA, Ma S, Cutler RG. Genomic 5-methyldeoxycytidine decreases with age. J Biol Chem 262: 9948-9951, 1987.
113. Xiang N, Zhao R, Song G, Zhong W. Selenite reactivates silenced genes by modifying DNA methylation and histones in prostate cancer cells. Carcinogenesis 29: 2175-2181, 2008.
114. Yenbutr P, Hilakivi-Clarke L, Passaniti A. Hypomethylation of an exon I estrogen receptor CpG island in spontaneous and carcinogeninduced mammary tumorigenesis in the rat. Mech Ageing Dev 106: 93-102, 1998.
115. Yokochi T, Robertson KD. Doxorubicin inhibits DNMT1, resulting in conditional apoptosis. Mol Pharmacol 66: 1415-1420, 2004.