The dynamic epigenome and its implications in toxicology

Toxicological Sciences

Volumn 100, Issue 1, 2007, Pages 7-23

  Szyf, Moshe ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

Anti cancer agents; Chromatin modification; Chromatin structure; DNA demethylase; DNA demethylation; DNA methylation; DNA methyltransferase; Epigenetics; Global hypomethylation; HDAC inhibitors; Histone acetylation; Histone acetyltransferase; Histone deacetylase; Histone methylation; Histone methyltransferase

Indexed keywords

ANTICONVULSIVE AGENT; CARCINOGEN; DNA METHYLTRANSFERASE; HISTONE ACETYLTRANSFERASE; HISTONE DEACETYLASE; HYDRALAZINE; METHIONINE; METHYL CPG BINDING PROTEIN 2; PHENOBARBITAL; PROCAINAMIDE; S ADENOSYLMETHIONINE; VALPROIC ACID; XENOBIOTIC AGENT;

ANIMAL BEHAVIOR; CANCER; CHROMATIN STRUCTURE; DEMETHYLATION; DNA METHYLATION; ENVIRONMENTAL EXPOSURE; ENZYME ACTIVITY; EPIGENETICS; GENE EXPRESSION; GENE SILENCING; GENETIC REGULATION; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HISTONE CODE; HUMAN; MATERNAL BEHAVIOR; MATERNAL CARE; NONHUMAN; PROGENY; REVIEW; RISK FACTOR; SOCIOECONOMICS; STRESS; TOXICOGENETICS;

ACETYLATION; ANIMALS; BEHAVIOR, ANIMAL; CELL NUCLEUS; CHROMATIN; CHROMATIN ASSEMBLY AND DISASSEMBLY; DNA METHYLATION; DNA MODIFICATION METHYLASES; EPIGENESIS, GENETIC; FEMALE; GENE EXPRESSION REGULATION; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENE EXPRESSION REGULATION, NEOPLASTIC; GENOMIC IMPRINTING; HISTONE ACETYLTRANSFERASES; HISTONE DEACETYLASES; HISTONES; HUMANS; MATERNAL BEHAVIOR; NEOPLASMS; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS; RISK ASSESSMENT; TOXICOGENETICS; VARIATION (GENETICS); XENOBIOTICS;

EID: 35448985442     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfm177     Document Type: Review

References (149)

1. Anway, M. D., Cupp, A. S., Uzumcu, M., and Skinner, M. K. (2005). Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308, 1466-1469.
2. Appanah, R., Dickerson, D. R., Goyal, P., Groudine, M., and Lorincz, M. C. (2007). An unmethylated 3′ promoter-proximal region is required for efficient transcription initiation. PLoS Genet. 3, e27.
3. Bachman, A. N., Curtin, G. M., Doolittle, D. J., and Goodman, J. I. (2006a). Altered methylation in gene-specific and GC-rich regions of DNA is progressive and nonrandom during promotion of skin tumorigenesis. Toxicol. Sci. 91, 406-418.
4. Bachman, A. N., Phillips, J. M., and Goodman, J. I. (2006b). Phenobarbital induces progressive patterns of GC-rich and gene-specific altered DNA methylation in the liver of tumor-prone B6C3F1 mice. Toxicol. Sci. 91, 303-405.
5. Barreto, G., Schafer, A., Marhold, J., Stach, D., Swaminathan, S. K., Handa, V., Doderlein, G., Maltry, N., Wu, W., Lyko, F., et al. (2007). Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature 445, 671-675.
6. Baylin, S. B., Esteller, M., Rountree, M. R., Bachman, K. E., Schuebel, K., and Herman, J. G. (2001). Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum. Mol. Genet. 10, 687-692.
7. Baylin, S. B., Herman, J. G., Graff, J. R., Vertino, P. M., and Issa, J. P. (1998). Alterations in DNA methylation: A fundamental aspect of neoplasia. Adv. Cancer Res. 72, 141-196.
8. Beck, S., Olek, A., and Walter, J. (1999). From genomics to epigenomics: A loftier view of life. Nat. Biotechnol. 17, 1144.
9. Bergmann, A., and Lane, M. E. (2003). HIDden targets of microRNAs for growth control. Trends Biochem. Sci. 28, 461-463.
10. Bhattacharya, S. K., Ramchandani, S., Cervoni, N., and Szyf, M. (1999). A mammalian protein with specific demethylase activity for mCpG DNA [see comments]. Nature 397, 579-583.
11. Bigey, P., Ramchandani, S., Theberge, I., Araujo, F. D., and Szyf, M. (2000). Transcriptional regulation of the human DNA Methyltransferase (dnmt1) gene. Gene 242, 407-418.
12. Bourc'his, D., Xu, G. L., Lin, C. S., Bollman, B., and Bestor, T. H. (2001). Dnmt3L and the establishment of maternal genomic imprints. Science 294, 2536-2539.
13. Bruniquel, D., and Schwartz, R. H. (2003). Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat. Immunol. 4, 235-240.
14. Bryk, M., Briggs, S. D., Strahl, B. D., Curcio, M. J., Allis, C. D., and Winston, F. (2001). Evidence that Set1, a factor required for methylation of histone H3, regulates rDNA silencing in S. cerevisiae by a Sir2-independent mechanism. Curr. Biol. 12, 165-170.
15. Bultman, S. J., Gebuhr, T. C., and Magnuson, T. (2005). A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development. Genes Dev. 19, 2849-2861.
16. Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., and Zhang, Y. (2002). Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298, 1039-1043.
17. Cao, R., and Zhang, Y. (2004). SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. Mol. Cell 15, 57-67.
18. Cervoni, N., and Szyf, M. (2001). Demethylase activity is directed by histone acetylation. J. Biol. Chem. 276, 40778-40787.
19. Chen, T., Hevi, S., Gay, F., Tsujimoto, N., He, T., Zhang, B., Ueda, Y., and Li, E. (2007). Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells. Nat. Genet. 39, 391-396.
20. Chrivia, J. C., Kwok, R. P., Lamb, N., Hagiwara, M., Montminy, M. R., and Goodman, R. H. (1993). Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365, 855-859.
21. Chuang, J. C., and Jones, P. A. (2007). Epigenetics and MicroRNAs. Pediatr Res. 61, 24R-29R.
22. Collas, P. (1998). Modulation of plasmid DNA methylation and expression in zebrafish embryos. Nucleic Acids Res. 26, 4454-4461.
23. Comb, M., and Goodman, H. M. (1990). CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Res. 18, 3975-3982.
24. Cornacchia, E., Golbus, J., Maybaum, J., Strahler, J., Hanash, S., and Richardson B. (1988). Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity. J. Immunol. 140, 2197-2200.
25. Counts, J. L., and Goodman, J. I. (1995a). Hypomethylation of DNA: A non-genotoxic mechanism involved in tumor promotion. Toxicol. Lett. 82-83, 663-672.
26. Counts, J. L., and Goodman, L. I. (1995b). Hypomethylation of DNA: A possible epigenetic mechanism involved in tumor promotion. Prog. Clin. Biol. Res. 391, 81-101.
27. D'Alessio, A. C., and Szyf, M. (2006). Epigenetic tete-a-tete: The bilateral relationship between chromatin modifications and DNA methylation. Biochem. Cell. Biol. 84, 463-476.
28. Detich, N., Bovenzi, V., and Szyf, M. (2003a). Valproate induces replication-independent active DNA demethylation. J. Biol. Chem. 278, 27586-27592.
29. Detich, N., Hamm, S., Just, G., Knox, J. D., and Szyf, M. (2003b). The methyl donor S-Adenosylmethionine inhibits active demethylation of DNA: A candidate novel mechanism for the pharmacological effects of S-Adenosylmethionine. J. Biol. Chem. 278, 20812-20820.
30. Detich, N., Theberge, J., and Szyf, M. (2002). Promoter-specific activation and demethylation by MBD2/demethylase. J. Biol. Chem. 277, 35791-35794.
31. Di Croce, L., Raker, V. A., Corsaro, M., Fazi, F., Fanelli, M., Faretta, M., Fuks, F., Lo Coco, F., Kouzarides, T., Nervi, C., et al. (2002). Methyl-transferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 295, 1079-1082.
32. Doi, T., Kawata, T., Tadano, N., Iijima, T., and Maekawa, A. (1989). Effect of vitamin B12 deficiency on S-adenosylmethionine metabolism in rats. J. Nutr. Sci. Vitaminol. (Tokyo) 35, 1-9.
33. Dolinoy, D. C., Das, R., Weidman, J. R., and Jirtle, R. L. (2007). Metastable epialleles, imprinting, and the fetal origins of adult diseases. Pediatr. Res. 61, 30R-37R.
34. Dolinoy, D.C., Weidman, J. R., Waterland, R. A., and Jirtle, R. L. (2006). Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ. Health Perspect. 114, 567-572.
35. Eckhardt, F., Lewin, J., Cortese, R., Rakyan, V. K., Attwood, J., Burger, M., Burton, J., Cox, T. V., Davies, R., Down, T. A., et al. (2006). DNA methylation profiling of human chromosomes 6, 20 and 22. Nat. Genet. 38, 1378-85.
36. Ehrlich, M. (2002). DNA methylation in cancer: Too much, but also too little. Oncogene 21, 5400-5413.
37. Feinberg, A. P., Gehrke, C. W., Kuo, K. C., and Ehrlich, M. (1988). Reduced genomic 5-methylcytosine content in human colonic neoplasia. Cancer Res. 48, 1159-1161.
38. Feinberg, A. P., and Vogelstein, B. (1983a). Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301, 89-92.
39. Feinberg, A. P., and Vogelstein, B. (1983b). Hypomethylation of ras oncogenes in primary human cancers. Biochem. Biophys. Res. Commun. 111, 47-54.
40. Fenech, M. (2001). The role of folic acid and Vitamin B12 in genomic stability of human cells. Mutat. Res. 475, 57-67.
41. Finch, J. T., Lutter, L. C., Rhodes, D., Brown, R. S., Rushton, B., Levitt, M., and Klug, A. (1977). Structure of nucleosome core particles of chromatin. Nature 269, 29-36.
42. Francis, D., Diorio, J., Liu, D., and Meaney, M. J. (1999). Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286, 1155-1158.
43. Fujita, N., Takebayashi, S., Okumura, K., Kudo, S., Chiba, T., Saya, H., and Nakao, M. (1999). Methylation-mediated transcriptional silencing in euchromatin by methyl-CpG binding protein MBD1 isoforms. Mol. Cell. Biol. 19, 6415-6426.
44. Fuks, F., Burgers, W. A., Brehm, A., Hughes-Davies, L., and Kouzarides, T. (2000). DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat. Genet. 24, 88-91.
45. Fuks, F., Hurd, P.J., Wolf, D., Nan, X., Bird, A. P., and Kouzarides, T. (2003). The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J. Biol. Chem. 278, 4035-4040.
46. Gibbons, R. J., Bachoo, S., Picketts, D. J., Aftimos, S., Asenbauer, B., Bergoffen, J., Berry, S. A., Dahl, N., Fryer, A., Keppler, K., et al. (1997). Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain. Nat. Genet. 17 146-148.
47. Goll, M. G., Kirpekar, F., Maggert, K. A., Yoder, J. A., Hsieh, C. L., Zhang, X., Golic, K. G., Jacobsen, S. E., and Bestor, T. H. (2006). Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311, 395-398.
48. Goto, K., Numata, M., Komura, J. I., Ono, T., Bestor, T. H., and Kondo, H. (1994). Expression of DNA methyltransferase gene in mature and immature neurons as well as proliferating cells in mice. Differentiation 56, 39-44.
49. Gottlicher, M., Minucci, S., Zhu, P., Kramer, O. H., Schimpf, A., Giavara, S., Sleeman, J. P., Lo Coco, F., Nervi, C., Pelicci, P. G., et al. (2001). Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J. 20, 6969-6978.
50. Grunstein, M. (1997). Histone acetylation in chromatin structure and transcription. Nature 389, 349-352.
51. Groudine, M., Eisenman, R., Gelinas, R., and Weintraub, H. (1983). Developmental aspects of chromatin structure and gene expression. Prog. Clin. Biol. Res. 134, 159-182.
52. Hayashi, H., Nagae, G., Tsutsumi, S., Kaneshiro, K., Kozaki, T., Kaneda, A., Sugisaki, H., and Aburatani, H. (2007). High-resolution mapping of DNA methylation in human genome using oligonucleotide tiling array. Hum. Genet. 120, 701-711.
53. Heinz, A., Higley, J. D., Gorey, J. G., Saunders, R. C., Jones, D. W., Hommer, D., Zajicek, K., Suomi, S. J., Lesch, K. P., Weinberger, D. R., et al. (1998). In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates. Am. J. Psychiatry 155, 1023-1028.
54. Hendrich, B., and Bird, A. (1998). Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol. Cell. Biol. 18, 6538-6547.
55. Henikoff, S., McKittrick, E., and Ahmad, K. (2004). Epigenetics, histone H3 variants, and the inheritance of chromatin states. Cold Spring Harb. Symp. Quant. Biol. 69, 235-243.
56. Inamdar, N. M., Ehrlich, K. C., and Ehrlich, M. (1991). CpG methylation inhibits binding of several sequence-specific DNA- binding proteins from pea, wheat, soybean and cauliflower. Plant. Mol. Biol. 17, 111-123.
57. Jenuwein, T. (2001). Re-SET-ting heterochromatin by histone methyltransferases. Trends Cell Biol. 11, 266-273.
58. Jenuwein, T., and Allis, C. D. (2001). Translating the histone code. Science 293, 1074-1080.
59. Jost, J. P. (1993). Nuclear extracts of chicken embryos promote an active demethylation of DNA by excision repair of 5-methyldeoxycytidine. Proc. Natl. Acad. Sci. U.S.A. 90, 4684-4688.
60. Kersh, E. N., Fitzpatrick, D. R., Murali-Krishna, K., Shires, J., Speck, S. H., Boss, J. M., and Ahmed, R. (2006). Rapid Demethylation of the IFN-{gamma} Gene occurs in memory but not naive CD8 T cells. J. Immunol. 176, 4083-4093.
61. Kramer, O. H., Gottlicher, M., and Heinzel, T. (2001). Histone deacetylase as a therapeutic target. Trends Endocrinol. Metab. 12, 294-300.
62. Kuendgen, A., Schmid, M., Schlenk, R., Knipp, S., Hildebrandt, B., Steidl, C., Germing, U., Haas, R., Dohner, H., and Gattermann, N. (2006). The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia. Cancer 106, 112-119.
63. Kuo, M. H., and Allis, C. D. (1998). Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays 20, 615-626.
64. Lachner, M., O'Carroll, D., Rea, S., Mechtler, K., and Jenuwein, T. (2001). Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116-120.
65. Laplante, P., Diorio, J., and Meaney, M. J. (2002). Serotonin regulates hippocampal glucocorticoid receptor expression via a 5-HT7 receptor. Brain Res. Dev. Brain Res. 139, 199-203.
66. Lee, D. Y., Hayes, J. J., Pruss, D., and Wolffe, A. P. (1993). A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72, 73-84.
67. Lee, T. I., Jenner, R. G., Boyer, L. A., Guenther, M. G., Levine, S. S., Kumar, R. M., Chevalier, B., Johnstone, S. E., Cole, M. F., Isono, K., et al. (2006). Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125, 301-313.
68. Levenson, J. M., Roth, T. L., Lubin, F. D., Miller, C. A., Huang, I. C., Desai, P., Malone, L. M., and Sweatt, J. D. (2006). Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J. Biol. Chem. 281, 15763-15773.
69. Li, E., Bestor, T. H., and Jaenisch, R. (1992). Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915-926.
70. Lichtenstein, M., Keini, G., Cedar, H., and Bergman, Y. (1994). B cell-specific demethylation: A novel role for the intronic kappa chain enhancer sequence. Cell 76, 913-923.
71. Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., Sharma, S., Pearson, D., Plotsky, P. M., and Meaney, M. J. (1997). Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 277 1659-1662.
72. Liu, H., Zhou, Y., Boggs, S. E., Belinsky, S. A., and Liu, J. (2007). Cigarette smoke induces demethylation of prometastatic oncogene synuclein-gamma in lung cancer cells by downregulation of DNMT3B. Oncogene.
73. Lucarelli, M., Fuso, A., Strom, R., and Scarpa, S. (2001). The dynamics of myogenin site-specific demethylation is strongly correlated with its expression and with muscle differentiation. J. Biol. Chem. 276 7500-7506.
74. Lyko, F., Ramsahoye, B. H., and Jaenisch, R. (2000). DNA methylation in Drosophila melanogaster. Nature 408, 538-540.
75. MacFarlane, M., Inoue, S., Kohlhaas, S. L., Majid, A. Harper, N., Kennedy, D. B., Dyer, M. J., and Cohen, G. M. (2005). Chronic lymphocytic leukemic cells exhibit apoptotic signaling via TRAIL-R1. Cell Death Differ. 12, 773-782.
76. MacLeod, A. R., Rouleau, J., and Szyf, M. (1995). Regulation of DNA methylation by the Ras signaling pathway. J. Biol. Chem. 270 11327-11337.
77. Marks, P. A., Richon, V. M., and Rifkind, R. A. (2000). Histone deacetylase inhibitors: Inducers of differentiation or apoptosis of transformed cells. J. Natl. Cancer Inst. 92, 1210-1216.
78. Marks, P. A., Sheffery, M., and Rifkind, R. A. (1985). Modulation of gene expression during terminal cell differentiation. Prog. Clin. Biol. Res. 191, 185-203.
79. McCormick, J. A., Lyons, V., Jacobson, M. D., Noble, J., Diorio, J., Nyirenda, M., Weaver, S., Ester, W., Yau, J. L., Meaney, M. J., et al. (2000). 5′-heterogeneity of glucocorticoid receptor messenger RNA is tissue specific: Differential regulation of variant transcripts by early-life events. Mol. Endocrinol. 14, 506-517.
80. Meaney, M. J., Aitken, D. H., and Sapolsky, R. M. (1987). Thyroid hormones influence the development of hippocampal glucocorticoid receptors in the rat: A mechanism for the effects of postnatal handling on the development of the adrenocortical stress response. Neuroendocrinology 45, 278-283.
81. Meaney, M. J., Diorio, J., Francis, D., Weaver, S., Yau, J., Chapman, K., and Seckl, J. R. (2000). Postnatal handling increases the expression of cAMP-inducible transcription factors in the rat hippocampus: The effects of thyroid hormones and serotonin. J. Neurosci. 20, 3926-3935.
82. Meaney, M. J., and Szyf, M. (2005a). Environmental programming of stress responses through DNA methylation: Life at the interface between a dynamic environment and a fixed genome. Dialogues Clin. Neurosci. 7, 103-123.
83. Meaney, M. J., and Szyf, M. (2005b). Maternal care as a model for experience-dependent chromatin plasticity? Trends Neurosci. 28 456-463.
84. Miller, C. A., and Sweatt, J. D. (2007). Covalent modification of DNA regulates memory formation. Neuron 53, 857-869.
85. Milutinovic, S., D'Alessio, A. C., Detich, N., and Szyf, M. (2007). Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes. Carcinogenesis 28, 560-571.
86. Nan, X., Campoy, F. J., and Bird, A. (1997). MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell 88, 471-481.
87. Narayan, A., Ji, W., Zhang, X. Y., Marrogi, A., Graff, J. R., Baylin, S. B., and Ehrlich, M. (1998). Hypomethylation of pericentromeric DNA in breast adenocarcinomas. Int. J. Cancer 77, 833-838.
88. Ng, H. H., Zhang, Y., Hendrich, B., Johnson, C. A., Turner, B. M., Erdjument-Bromage, H., Tempst, P., Reinberg, D., and Bird, A. (1999a). MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat. Genet. 23, 58-61.
89. Ng, H. H., Zhang, Y., Hendrich, B., Johnson, C. A., Turner, B. M., Erdjument-Bromage, H., Tempst, P., Reinberg, D., and Bird, A. (1999b). MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex [see comments]. Nat. Genet. 23, 58-61.
90. Ogryzko, V. V., Schiltz, R. L., Russanova, V., Howard, B. H., and Nakatani, Y. (1996). The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87, 953-959.
91. Ohm, J. E., McGarvey, K. M., Yu, X., Cheng, L., Schuebel, K. E., Cope, L., Mohammad, H. P., Chen, W., Daniel, V. C., Yu, W., et al. (2007). A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat. Genet. 39, 237-242.
92. Okano, M., Bell, D. W., Flaber, D. A., and Li, E. (1999). DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247-257.
93. Okano, M., Xie, S., and Li, E. (1998). Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltranferases [letter]. Nat. Genet. 19, 219-220.
94. Oswald, J., Engemann, S., Lane, N., Mayer, W., Olek, A., Fundele, R., Dean, W., Reik, W., and Walter, J. (2000). Active demethylation of the paternal genome in the mouse zygote. Curr. Biol. 10, 475-478.
95. Pakneshan, P., Szyf, M., Farias-Eisner, R., and Rabbani, S. A. (2004). Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis. J. Biol. Chem. 279 31735-31744.
96. Pakneshan, P., Szyf, M., and Rabbani, S. A. (2005). Methylation and inhibition of uPA expression by RAS oncogene: Divergenee of growth control and invasion in breast cancer cells. Carcinogenesis 26 557-564.
97. Perry, M., and Chalkley, R. (1982). Histone acetylation increases the solubility of chromatin and occurs sequentially over most of the chromatin. A novel model for the biological role of histone acetylation. J. Biol. Chem. 257, 7336-7347.
98. Picketts, D. J., Higgs, D. R., Bachoo, S., Blake, D. J., Quarrell, O. W. and Gibbons,R. J. (1996). ATRX encodes a novel member of the SNF2 family of proteins: Mutations point to a common mechanism underlying the ATR-X syndrome. Hum. Mol. Genet. 5, 1899-1907.
99. Rai, K., Chidester, S., Zavala, C. V., Manos, E. J., James, S. R., Karpf, A. R., Jones, D. A., and Cairns, B. R. (2007). Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish. Genes Dev. 21, 261-266.
100. Ramain, P., Bourouis, M., Dretzen, G., Richards, G. Sobkowiak, A., and Bellard, M. (1986). Changes in the chromatin structure of Drosophila glue genes accompany developmental cessation of transcription in wild type and transformed strains. Cell 45, 545-553.
101. Rambaldi, A., and Gluud, C. (2006). S-adenosyl-L-methionine for alcoholic liver diseases. Cochrane Database Syst. Rev. CD002235.
102. Ramchandani, S., Bhattacharya, S. K., Cervoni, N., and Szyf, M. (1999a). DNA methylation is a reversible biological signal. Proc. Natl. Acad. Sci. U.S.A. 96, 6107-6112.
103. Ramchandani, S., Bhattacharya, S. K., Cervoni, N., and Szyf, M. (1999b): DNA methylation is a reversible biological signal [see comments]. Proc. Natl. Acad. Sci. U.S.A. 96, 6107-6112.
104. Ramsahoye, B. H., Biniszkiewicz, D., Lyko, F., Clark, V., Bird, A. P., and Jaenisch, R. (2000). Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc. Natl. Acad. Sci. U.S.A. 97, 5237-5242.
105. Rauch, T., Wang, Z., Zhang, X., Zhong, X., Wu, X., Lau, S. K., Kernstine, K. H., Riggs, A. D., and Pfeifer, G. P. (2007). Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay. Proc. Natl. Acad. Sci. U. S. A. 104, 5527-5532.
106. Razin, A. (1998). CpG methylation, chromatin structure and gene silencing- a three-way connection. EMBO J 17, 4905-4908.
107. Razin, A., and Cedar, H. (1977). Distribution of 5-methylcytosine in chromatin. Proc. Natl. Acad. Sci. U.S.A. 74, 2725-2728.
108. Razin, A., and Riggs, A. D. (1980). DNA methylation and gene function. Science 210, 604-610.
109. Razin, A., and Szyf, M. (1984). DNA methylation patterns. Formation and function. Biochim. Biophys. Acta 782, 331-342.
110. Rountree, M. R.,Bachman, K. E., and Baylin, S. B. (2000). DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat. Genet. 25, 269-277.
111. Saito, Y., and Jones, P. A. (2006). Epigenetic activation of tumor suppressor microRNAs in human cancer cells. Cell Cycle 5, 2220-2222.
112. Sarma, K., and Reinberg, D. (2005). Histone variants meet their match. Nat. Rev. Mol. Cell Biol. 6, 139-149.
113. Schlesinger, Y., Straussman, R., Keshet, I., Farkash, S., Hecht, M., Zimmerman, J., Eden, E., Yakhini, Z., Ben-Shushan, E., Reubinoff, B. E., et al. (2001). Polycomb-mediated methylation on Lys27 of histone H3 premarks genes for de novo methylation in cancer. Nat. Genet. 39, 232-236.
114. Schwartz, Y. B., and Pirrotta, V. (2007). Polycomb silencing mechanisms and the management of genomic programmes. Nat. Rev. Genet. 8 9-22.
115. Selhub, J. (2002). Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J. Nutr. Health Aging 6, 39-42.
116. Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J. R., Cole, P. A., Casero, R. A., and Shi, Y. (2004). Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119, 941-953.
117. Shilatifard, A. (2006). Chromatin Modifications by Methylation and Ubiquitination: Implications in the Regulation of Gene Expression. Annu. Rev. Biochem. 2432, 243-269.
118. Shukeir, N., Pakneshan, P., Chen, G., Szyf, M., and Rabbani, S. A. (2006). Alteration of the methylation status of tumor-promoting genes decreases prostate cancer cell invasiveness and tumorigenesis in vitro and in vivo. Cancer Res. 66, 9202-9210.
119. Simonini, M. V., Camargo, L. M., Dong, E., Maloku, E., Veldic, M., Costa, E., and Guidotti, A, (2006). The benzamide MS-275 is a potent, long-lasting brain region-selective inhibitor of histone deacetylases. Proc. Natl. Acad. Sci. U.S.A. 103, 1587-1592.
120. Sinha, I., Wiren, M., and Ekwall, K. (2006). Genome-wide patterns of histone modifications in fission yeast. Chromosome Res. 14, 95-105.
121. Slack, A., Cervoni, N., Pinard, M., and Szyf, M. (1999). DNA methyltransferase is a downstream effector of cellular transformation triggered by simian virus 40 large T antigen. J. Biol. Chem. 274, 10105-10112.
122. Smallwood, A., Esteve, P. O., Pradhan, S., and Carey, M. (2007). Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes Dev. 21, 1169-1178.
123. Stein, R., Sciaky-Gallili, N., Razin, A., and Cedar, H. (1983). Pattern of methylation of two genes coding for housekeeping functions. Proc. Natl. Acad. Sci. U.S.A. 80, 2422-2426.
124. Szyf, M. (2001). Towards a pharmacology of DNA methylation. Trends Pharmacol. Sci. 22, 350-354.
125. Szyf, M. (2006). Targeting DNA methylation in cancer. Bull. Cancer 93, 961-972.
126. Szyf, M., Knox, D. J., Milutinovic, S., Slack, A. D., and Araujo, F. D. (2000). How does DNA methyltransferase cause oncogenic transformation? Ann. N.Y. Acad. Sci. 910, 156-174; discussion 175-177.
127. Szyf, M., Schimmer, B. P., and Seidman, J. G. (1989). Nucleotide-sequence-specific de novo methylation in a somatic routine cell line. Proc. Natl. Acad. Sci. U.S.A. 86, 6853-6857.
128. Tremolizzo, L., Carboni, G., Ruzicka, W. B., Mitchell, C. P., Sugaya, I., Tueting, P., Sharma, R., Grayson, D. R., Costa, E., and Guidotti, A. (2002). An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability. Proc. Natl. Acad. Sci. U.S.A. 99, 17095-17100.
129. Tsukada, Y., Fang, J., Erdjument-Bromage, H., Warren, M. E., Borchers, C. H., Tempst, P., and Zhang, Y. (2006). Histone demethylation by a family of JmjC domain-containing proteins. Nature 439, 811-816.
130. Urieli-Shoval, S., Gruenbaum, Y., Sedat, J., and Razin, A. (1982). The absence of detectable methylated bases in Drosophila melanogaster DNA. FEBS Lett. 146, 148-152.
131. Varga-Weisz, P. D., and Becker, P. B. (2006). Regulation of higher-order chromatin structures by nucleosome-remodelling factors. Curr. Opin. Genet. Dev. 16, 151-156.
132. Veldic, M., Guidotti, A., Maloku, E., Davis, J. M., and Costa, E. (2005). In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proc. Natl. Acad. Sci. U.S.A. 102, 2152-2157.
133. Vilain, A., Apiou, F., Dutrillaux, B., and Malfoy, B. (1998). Assignment of candidate DNA methyltransferase gene (DNMT2) to human chromosome band 10p15.1 by in situ hybridization. Cytogenet. Cell Genet. 82, 120.
134. Vire, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J. M., et al. (2005). The Polycomb group protein EZH2 directly controls DNA methylation. Nature.
135. Vire, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J. M., et al. (2006). The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439, 871-874.
136. Vo, N., Klein, M. E., Varlamova, O., Keller, D. M., Yamamoto, T., Goodman, R. H., and Impey, S. (2005). A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc. Natl. Acad. Sci. U.S.A. 102, 16426-16431.
137. Wade, P. A., Pruss, D., and Wolffe, A. P. (1997). Histone acetylation: Chromatin in action. Trends Biochem. Sci. 22, 128-132.
138. Waterland, R. A., and Jirtle, R. L. (2003). Transposable elements: Targets for early nutritional effects on epigenetic gene regulation. Mol. Cell. Biol. 23, 5293-5300.
139. Weaver, I. C., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., and Meaney, M. J. (2004a). Epigenetic programming by maternal behavior. Nat. Neurosci. 7 847-854.
140. Weaver, I. C, Champagne, F. A., Brown, S. E., Dymov, S., Sharma, S., Meaney, M. J., and Szyf, M. (2005). Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: Altering epigenetic marking later in life. J. Neurosci. 25, 11045-11054.
141. Weaver, I. C., D'Alessio, A. C., Brown, S. E., Hellstrom, I. C., Dymov, S., Sharma, S., Szyf, M., and Meaney, M. J. (2007). The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: Altering epigenetic marks by Immediate-early genes. J. Neurosci. 27, 1756-1768.
142. Weaver, I. C., Diorio, J., Seckl, J. R., Szyf, M., and Meaney, M. J. (2004b). Early environmental regulation of hippocampal glucocorticoid receptor gene expression: Characterization of intracellular mediators and potential genomic target sites. Ann. N.Y. Acad. Sci. 1024 182-212.
143. Weaver, I. C., Meaney, M. J., and Szyf, M. (2006). Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proc. Natl. Acad., Sci. U.S.A. 103, 3480-3485.
144. Weidle, U. H., and Grossmann, A. (2000). Inhibition of histone deacetylases: A new strategy to target epigenetic modifications for anticancer treatment. Anticancer Res. 20, 1471-1485.
145. Widschwendter, M., Fiegl, H., Egle, P., Mueller-Holzner, E., Spizzo, G., Marth, C., Weisenberger, D. J., Campan, M., Young, J., Jacobs, I., et al. (2007). Epigenetic stem cell signature in cancer. Nat. Genet. 39, 157-158.
146. Wolffe, A. P. (1996). Histone deacetylase: A regulator of transcription. Science 272, 371-372.
147. Zhang, B., Pan, X., Cobb, G. P., and Anderson, T. A. (2007). microRNAs as oncogenes and tumor suppressors. Dev. Biol. 302, 1-12.
148. Zhang, X., Yazaki, J., Sundaresan, A., Cokus, S., Chan, S. W., Chen, H., Henderson, I. R., Shinn, P., Pellegrini, M., Jacobsen, S. E., et al. (2006). Genome-wide High-Resolution Mapping and Functional Analysis of DNA Methylation in Arabidopsis. Cell 126, 1189-1201.
149. Zhu, B., Zheng, Y., Hess, D., Angliker, H., Schwarz, S., Siegmann, M., Thiry, S., and Jost, J. P. (2000). 5-methylcytosine-DNA glycosylase activity is present in a cloned G/T mismatch DNA glycosylase associated with the chicken embryo DNA demethylation complex. Proc. Natl. Acad. Sci. U.S.A. 97, 5135-5139.