Epigenetics in human disease and prospects for epigenetic therapy (original) (raw)

• Holliday, R. & Pugh, J. E. DNA modification mechanisms and gene activity during development. Science 187, 226–232 (1975).
  ADS CAS PubMed Google Scholar
• Riggs, A. D. X inactivation, differentiation, and DNA methylation. Cytogenet. Cell Genet. 14, 9–25 (1975).
  CAS PubMed Google Scholar
• Takai, D. & Jones, P. A. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc. Natl Acad. Sci. USA 99, 3740–3745 (2002).
  ADS CAS PubMed PubMed Central Google Scholar
• Jones, P. A. & Baylin, S. B. The fundamental role of epigenetic events in cancer. Nature Rev. Genet. 3, 415–428 (2002).
  CAS PubMed Google Scholar
• Lachner, M. & Jenuwein, T. The many faces of histone lysine methylation. Curr. Opin. Cell Biol. 14, 286–298 (2002).
  CAS PubMed Google Scholar
• Fischle, W., Wang, Y. & Allis, C. D. Binary switches and modification cassettes in histone biology and beyond. Nature 425, 475–479 (2003).
  ADS CAS PubMed Google Scholar
• Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41–45 (2000).
  ADS CAS PubMed Google Scholar
• Tamaru, H. & Selker, E. U. A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414, 277–283 (2001).
  ADS CAS PubMed Google Scholar
• Jackson, J. P., Lindroth, A. M., Cao, X. & Jacobsen, S. E. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature 416, 556–560 (2002).
  ADS CAS PubMed Google Scholar
• Malagnac, F., Bartee, L. & Bender, J. An Arabidopsis SET domain protein required for maintenance but not establishment of DNA methylation. EMBO J. 21, 6842–6852 (2002).
  CAS PubMed PubMed Central Google Scholar
• Johnson, L., Cao, X. & Jacobsen, S. Interplay between two epigenetic marks. DNA methylation and histone H3 lysine 9 methylation. Curr. Biol. 12, 1360–1367 (2002).
  CAS PubMed Google Scholar
• Soppe, W. J. et al. DNA methylation controls histone H3 lysine 9 methylation and heterochromatin assembly in Arabidopsis. EMBO J. 21, 6549–6559 (2002).
  CAS PubMed PubMed Central Google Scholar
• Tariq, M. et al. Erasure of CpG methylation in Arabidopsis alters patterns of histone H3 methylation in heterochromatin. Proc. Natl Acad. Sci. USA 100, 8823–8827 (2003).
  ADS CAS PubMed PubMed Central Google Scholar
• Lehnertz, B. et al. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr. Biol. 13, 1192–1200 (2003).
  CAS PubMed Google Scholar
• Nan, X. et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393, 386–389 (1998).
  Article ADS CAS PubMed Google Scholar
• Fuks, F. et al. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J. Biol. Chem. 278, 4035–4040 (2003).
  CAS PubMed Google Scholar
• Fuks, F., Burgers, W. A., Brehm, A., Hughes-Davies, L. & Kouzarides, T. DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nature Genet. 24, 88–91 (2000).
  CAS PubMed Google Scholar
• Hall, I. M. et al. Establishment and maintenance of a heterochromatin domain. Science 297, 2232–2237 (2002).
  ADS CAS PubMed Google Scholar
• Volpe, T. A. et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833–1837 (2002).
  ADS CAS PubMed Google Scholar
• Zilberman, D., Cao, X. & Jacobsen, S. E. ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation. Science 299, 716–719 (2003).
  ADS CAS PubMed Google Scholar
• Rougeulle, C. & Heard, E. Antisense RNA in imprinting: spreading silence through Air. Trends Genet. 18, 434–437 (2002).
  CAS PubMed Google Scholar
• Panning, B. & Jaenisch, R. RNA and the epigenetic regulation of X chromosome inactivation. Cell 93, 305–308 (1998).
  CAS PubMed Google Scholar
• Tufarelli, C. et al. Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Nature Genet. 203, 157–165 (2003).
  Google Scholar
• Okano, M., Bell, D. W., Haber, D. A. & Li, E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247–257 (1999).
  CAS PubMed Google Scholar
• Amir, R. E. et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genet. 23, 185–188 (1999).
  CAS PubMed Google Scholar
• Klose, R. & Bird, A. Molecular biology. MeCP2 repression goes nonglobal. Science 302, 793–795 (2003).
  CAS PubMed Google Scholar
• Chen, W. G. et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302, 885–889 (2003).
  ADS CAS PubMed Google Scholar
• Martinowich, K. et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302, 890–893 (2003).
  ADS CAS PubMed Google Scholar
• Kane, M. F. et al. 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, 808–811 (1997).
  CAS PubMed Google Scholar
• Gazzoli, I., Loda, M., Garber, J., Syngal, S. & Kolodner, R. D. A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the MLH1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instability-high tumor. Cancer Res. 62, 3925–3928 (2002).
  CAS PubMed Google Scholar
• Suter, C. M., Martin, D. I. & Ward, R. L. Germline epimutation of MLH1 in individuals with multiple cancers. Nature Genet. advance online publication 4 April 2004 (doi:10.1038/ng1342).
• Jones, P. A. & Laird, P. W. Cancer epigenetics comes of age. Nature Genet. 21, 163–167 (1999).
  CAS PubMed Google Scholar
• Hake, S. B., Xiao, A. & Allis, C. D. Linking the epigenetic ‘language’ of covalent histone modifications to cancer. Br. J. Cancer 90, 761–769 (2004).
  CAS PubMed PubMed Central Google Scholar
• Grignani, F. et al. Fusion proteins of the retinoic acid receptor-α recruit histone deacetylase in promyelocytic leukaemia. Nature 391, 815–818 (1998).
  ADS CAS PubMed Google Scholar
• Jones, L. K. & Saha, V. Chromatin modification, leukaemia and implications for therapy. Br. J. Haematol. 118, 714–727 (2002).
  PubMed Google Scholar
• Roberts, C. W. & Orkin, S. H. The SWI/SNF complex — chromatin and cancer. Nature Rev. Cancer 4, 133–142 (2004).
  CAS Google Scholar
• Wilson, V. L. & Jones, P. A. DNA methylation decreases in aging but not in immortal cells. Science 220, 1055–1057 (1983).
  ADS CAS PubMed Google Scholar
• Richardson, B. C. Role of DNA methylation in the regulation of cell function: autoimmunity, aging and cancer. J. Nutr. 132, 2401S–2405S (2002).
  CAS PubMed Google Scholar
• Issa, J. P. CpG-island methylation in aging and cancer. Curr. Top. Microbiol. Immunol. 249, 101–118 (2000).
  CAS PubMed Google Scholar
• Beaudet, A. L. & Jiang, Y. H. A rheostat model for a rapid and reversible form of imprinting-dependent evolution. Am. J. Hum. Genet. 70, 1389–1397 (2002).
  CAS PubMed PubMed Central Google Scholar
• Laird, P. W. et al. Suppression of intestinal neoplasia by DNA hypomethylation. Cell 81, 197–205 (1995).
  CAS PubMed Google Scholar
• Sorm, F., Piskala, A., Cihak, A. & Vesely, J. 5-Azacytidine, a new, highly effective cancerostatic. Experientia 20, 202–203 (1964).
  CAS PubMed Google Scholar
• Constantinides, P. G., Jones, P. A. & Gevers, W. Functional striated muscle cells from non-myoblast precursors following 5-azacytidine treatment. Nature 267, 364–366 (1977).
  ADS CAS PubMed Google Scholar
• Jones, P. A. & Taylor, S. M. Cellular differentiation, cytidine analogs and DNA methylation. Cell 20, 85–93 (1980).
  CAS PubMed Google Scholar
• Zhou, L. et al. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J. Mol. Biol. 321, 591–599 (2002).
  CAS PubMed PubMed Central Google Scholar
• Michalowsky, L. A. & Jones, P. A. Differential nuclear protein binding to 5-azacytosine-containing DNA as a potential mechanism for 5-aza-2′-deoxycytidine resistance. Mol. Cell. Biol. 7, 3076–3083 (1987).
  CAS PubMed PubMed Central Google Scholar
• Issa, J. P. et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103, 1635–1640 (2004).
  CAS PubMed Google Scholar
• Saunthararajah, Y. et al. Effects of 5-aza-2′-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease. Blood 102, 3865–3870 (2003).
  CAS PubMed Google Scholar
• Cheng, J. C. et al. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J. Natl Cancer Inst. 95, 399–409 (2003).
  CAS PubMed Google Scholar
• Lin, X. et al. Reversal of GSTP1 CpG island hypermethylation and reactivation of pi-class glutathione _S_-transferase (GSTP1) expression in human prostate cancer cells by treatment with procainamide. Cancer Res. 61, 8611–8616 (2001).
  CAS PubMed Google Scholar
• Fang, M. Z. et al. Tea polyphenol (–)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 63, 7563–7570 (2003).
  CAS PubMed Google Scholar
• Pina, I. C. et al. Psammaplins from the sponge Pseudoceratina purpurea: inhibition of both histone deacetylase and DNA methyltransferase. J. Org. Chem. 68, 3866–3873 (2003).
  CAS PubMed Google Scholar
• Yan, L. et al. Specific inhibition of DNMT1 by antisense oligonucleotides induces re-expression of estrogen receptor-α (ER) in ER-negative human breast cancer cell lines. Cancer Biol. Ther. 2, 552–556 (2003).
  CAS PubMed Google Scholar
• Xiao, H., Hasegawa, T. & Isobe, K. Both Sp1 and Sp3 are responsible for p21waf1 promoter activity induced by histone deacetylase inhibitor in NIH3T3 cells. J. Cell. Biochem. 73, 291–302 (1999).
  CAS PubMed Google Scholar
• Marks, P. A., Miller, T. & Richon, V. M. Histone deacetylases. Curr. Opin. Pharmacol. 3, 344–351 (2003).
  CAS PubMed Google Scholar
• Jahangeer, S., Elliott, R. M. & Henneberry, R. C. β-Adrenergic receptor induction in HeLa cells: synergistic effect of 5-azacytidine and butyrate. Biochem. Biophys. Res. Commun. 108, 1434–1440 (1982).
  CAS PubMed Google Scholar
• Ginder, G. D., Whitters, M. J. & Pohlman, J. K. Activation of a chicken embryonic globin gene in adult erythroid cells by 5-azacytidine and sodium butyrate. Proc. Natl Acad. Sci. USA 81, 3954–3958 (1984).
  ADS CAS PubMed PubMed Central Google Scholar
• Cameron, E. E., Bachman, K. E., Myohanen, S., Herman, J. G. & Baylin, S. B. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nature Genet. 21, 103–107 (1999).
  CAS PubMed Google Scholar
• Suzuki, H. et al. A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nature Genet. 31, 141–149 (2002).
  CAS PubMed Google Scholar
• Yamashita, K. et al. Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma. Cancer Cell 2, 485–495 (2002).
  CAS PubMed Google Scholar
• Belinsky, S. A. et al. Inhibition of DNA methylation and histone deacetylation prevents murine lung cancer. Cancer Res. 63, 7089–7093 (2003).
  CAS PubMed Google Scholar
• Claus, R. & Lubbert, M. Epigenetic targets in hematopoietic malignancies. Oncogene 22, 6489–6496 (2003).
  CAS PubMed Google Scholar
• Plumb, J. A., Strathdee, G., Sludden, J., Kaye, S. B. & Brown, R. Reversal of drug resistance in human tumor xenografts by 2′-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter. Cancer Res. 60, 6039–6044 (2000).
  CAS PubMed Google Scholar
• Karpf, A. R. & Jones, D. A. Reactivating the expression of methylation silenced genes in human cancer. Oncogene 21, 5496–5503 (2002).
  CAS PubMed Google Scholar
• Weber, J. et al. Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-aza-2′-deoxycytidine. Cancer Res. 54, 1766–1771 (1994).
  CAS PubMed Google Scholar
• Laird, P. W. The power and the promise of DNA methylation markers. Nature Rev. Cancer 3, 253–266 (2003).
  CAS Google Scholar
• Liang, G., Gonzales, F. A., Jones, P. A., Orntoft, T. F. & Thykjaer, T. Analysis of gene induction in human fibroblasts and bladder cancer cells exposed to the methylation inhibitor 5-aza-2′-deoxycytidine. Cancer Res. 62, 961–966 (2002).
  CAS PubMed Google Scholar
• Mohandas, T., Sparkes, R. S. & Shapiro, L. J. Reactivation of an inactive X human chromosome: evidence for X inactivation by DNA methylation. Science 211, 393–396 (1981).
  ADS CAS PubMed Google Scholar
• Wolf, S. F. & Migeon, B. R. Studies of X chromosome DNA methylation in normal human cells. Nature 295, 667–671 (1982).
  ADS CAS PubMed Google Scholar
• Eversole-Cire, P. et al. Activation of an imprinted Igf 2 gene in mouse somatic cell cultures. Mol. Cell. Biol. 13, 4928–4938 (1993).
  CAS PubMed PubMed Central Google Scholar
• Jackson-Grusby, L., Laird, P. W., Magge, S. N., Moeller, B. J. & Jaenisch, R. Mutagenicity of 5-aza-2′-deoxycytidine is mediated by the mammalian DNA methyltransferase. Proc. Natl Acad. Sci. USA 94, 4681–4685 (1997).
  ADS CAS PubMed PubMed Central Google Scholar
• Carr, B. I., Rahbar, S., Asmeron, Y., Riggs, A. & Winberg, C. D. Carcinogenicity and haemoglobin synthesis induction by cytidine analogues. Br. J. Cancer 57, 395–402 (1988).
  CAS PubMed PubMed Central Google Scholar
• Sato, N. et al. Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinoma. Cancer Res. 63, 4158–4166 (2003).
  CAS PubMed Google Scholar
• Yang, A. S., Estecio, M. R., Garcia-Manero, G., Kantarjian, H. M. & Issa, J. P. Comment on ‘Chromosomal instability and tumors promoted by DNA hypomethylation’ and ‘Induction of tumors in nice by genomic hypomethylation’. Science 302, 1153 (2003).
  CAS PubMed Google Scholar
• Lubbert, M. et al. Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Br. J. Haematol. 114, 349–357 (2001).
  CAS PubMed Google Scholar
• Karpf, A. R., Moore, B. C., Ririe, T. O. & Jones, D. A. Activation of the p53 DNA damage response pathway after inhibition of DNA methyltransferase by 5-aza-2′-deoxycytidine. Mol. Pharmacol. 59, 751–757 (2001).
  CAS PubMed Google Scholar
• Jackson-Grusby, L. et al. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nature Genet. 27, 31–39 (2001).
  CAS PubMed Google Scholar
• Peterson, E. J., Bogler, O. & Taylor, S. M. p53-mediated repression of DNA methyltransferase 1 expression by specific DNA binding. Cancer Res. 63, 6579–6582 (2003).
  CAS PubMed Google Scholar
• Juttermann, R., Li, E. & Jaenisch, R. Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc. Natl Acad. Sci. USA 91, 11797–11801 (1994).
  ADS CAS PubMed PubMed Central Google Scholar
• Esteller, M., Corn, P. G., Baylin, S. B. & Herman, J. G. A gene hypermethylation profile of human cancer. Cancer Res. 61, 3225–3229 (2001).
  CAS PubMed Google Scholar
• Cui, H. et al. Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 299, 1753–1755 (2003).
  ADS CAS PubMed Google Scholar
• Gibbons, R. J. & Higgs, D. R. Molecular-clinical spectrum of the ATR-X syndrome. Am. J. Med. Genet. 97, 204–212 (2000).
  CAS PubMed Google Scholar
• Oostra, B. A. & Willemsen, R. The X chromosome and fragile X mental retardation. Cytogenet. Genome Res. 99, 257–264 (2002).
  CAS PubMed Google Scholar
• Ehrlich, M. The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease. Clin. Immunol. 109, 17–28 (2003).
  CAS PubMed Google Scholar
• Nicholls, R. D., Saitoh, S. & Horsthemke, B. Imprinting in Prader–Willi and Angelman syndromes. Trends Genet. 14, 194–200 (1998).
  CAS PubMed Google Scholar
• Goldstone, A. P. Prader–Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol. Metab. 15, 12–20 (2004).
  CAS PubMed Google Scholar
• Maher, E. R. & Reik, W. Beckwith–Wiedemann syndrome: imprinting in clusters revisited. J. Clin. Invest. 105, 247–252 (2000).
  CAS PubMed PubMed Central Google Scholar
• Feinberg, A. P. & Tycko, B. The history of cancer epigenetics. Nature Rev. Cancer 4, 143–153 (2004).
  CAS Google Scholar
• Soejima, H. et al. Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer. Oncogene published online 8 March 2004 (doi:10.1038/sj.onc.1207576).
• Ausio, J., Levin, D. B., De Amorim, G. V., Bakker, S. & Macleod, P. M. Syndromes of disordered chromatin remodeling. Clin. Genet. 64, 83–95 (2003).
  CAS PubMed Google Scholar
• Yoder, J. A., Walsh, C. P. & Bestor, T. H. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 13, 335–340 (1997).
  CAS PubMed Google Scholar
• Nguyen, C. T., Gonzales, F. A. & Jones, P. A. Altered chromatin structure associated with methylation-induced gene silencing in cancer cells: correlation of accessibility, methylation, MeCP2 binding and acetylation. Nucleic Acids Res. 29, 4598–4606 (2001).
  CAS PubMed PubMed Central Google Scholar
• Bachman, K. E. et al. Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene. Cancer Cell 3, 89–95 (2003).
  CAS PubMed Google Scholar
• El-Osta, A. & Wolffe, A. P. DNA methylation and histone deacetylation in the control of gene expression: basic biochemistry to human development and disease. Gene Expr. 9, 63–75 (2000).
  CAS PubMed Google Scholar
• Nguyen, C. T. et al. Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2′-deoxycytidine. Cancer Res. 62, 6456–6461 (2002).
  CAS PubMed Google Scholar