Van Speybroeck, L. From epigenesis to epigenetics: the case of C. H. Waddington. Ann. NY Acad. Sci. 981, 61–81 (2002).
Debaun, M. R. & Feinberg, A. P. in Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis (ed. Epstein, C. J.) 758–765 (Oxford Univ. Press, Oxford, USA, 2004).
Niemitz, E. L. et al. Microdeletion of LIT1 in familial Beckwith–Wiedemann syndrome. Am. J. Hum. Genet. 75, 844–849 (2004).
Sparago, A. et al. Microdeletions in the human H19 DMR result in loss of IGF2 imprinting and Beckwith–Wiedemann syndrome. Nature Genet. 36, 958–960 (2004).
DeBaun, M. R. et al. Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith–Wiedemann syndrome with cancer and birth defects. Am. J. Hum. Genet. 70, 604–611 (2002).
Diaz-Meyer, N., Yang, Y., Sait, S. N., Maher, E. R. & Higgins, M. J. Alternative mechanisms associated with silencing of CDKN1C in Beckwith–Wiedemann syndrome. J. Med. Genet. 42, 648–655 (2005).
Horsthemke, B. & Buiting, K. Imprinting defects on human chromosome 15. Cytogenet. Genome Res. 113, 292–299 (2006).
Lalande, M. Imprints of disease at GNAS1. J. Clin. Invest. 107, 793–794 (2001).
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).
Bienvenu, T. & Chelly, J. Molecular genetics of Rett syndrome: when DNA methylation goes unrecognized. Nature Rev. Genet. 7, 415–426 (2006).
Xu, G. L. et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402, 187–191 (1999).
Blanco-Betancourt, C. E. et al. Defective B-cell-negative selection and terminal differentiation in the ICF syndrome. Blood 103, 2683–2690 (2004).
Gibbons, R. J. & Higgs, D. R. Molecular-clinical spectrum of the ATR-X syndrome. Am. J. Med. Genet. 97, 204–212 (2000).
Petrif, F. et al. Rubinstein–Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376, 348–351 (2002).
Feinberg, A. P. & Vogelstein, B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301, 89–92 (1983).
Wilson, A. S., Power, B. E. & Molloy, P. L. DNA hypomethylation and human diseases. Biochim. Biophys. Acta 1775, 138–162 (2007).
Feinberg, A. P. & Tycko, B. The history of cancer epigenetics. Nature Rev. Cancer 4, 143–153 (2004).
Brueckner, B. et al. The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res. 67, 1419–1423 (2007).
Wu, H. et al. Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature 438, 981–987 (2005).
Greger, V., Passarge, E., Hopping, W., Messmer, E. & Horsthemke, B. Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum. Genet. 83, 155–158 (1989).
Jones, P. A. & Baylin, S. B. The fundamental role of epigenetic events in cancer. Nature Rev. Genet. 3, 415–428 (2002).
Costello, J. F. et al. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nature Genet. 24, 132–138 (2000).
Esteller, M., Corn, P. G., Baylin, S. B. & Herman, J. G. A gene hypermethylation profile of human cancer. Cancer Res. 61, 3225–3229 (2001).
Frigola, J. et al. Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band. Nature Genet. 38, 540–549 (2006).
Hattori, N. et al. Preference of DNA methyltransferases for CpG islands in mouse embryonic stem cells. Genome Res. 14, 1733–1740 (2004).
Weber, M. et al. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nature Genet. 37, 853–862 (2005).
Gius, D. et al. Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach. Cancer Cell 6, 361–371 (2004).
Scrable, H. et al. A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting. Proc. Natl Acad. Sci. USA 86, 7480–7484 (1989).
Rainier, S. et al. Relaxation of imprinted genes in human cancer. Nature 362, 747–749 (1993).
Ogawa, O. et al. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature 362, 749–751 (1993).
Feinberg, A. P. Genomic imprinting and gene activation in cancer. Nature Genet. 4, 110–113 (1993).
Kondo, M. et al. Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene 10, 1193–1198 (1995).
van Roozendaal, C. E. et al. Loss of imprinting of IGF2 and not H19 in breast cancer, adjacent normal tissue and derived fibroblast cultures. FEBS Lett. 437, 107–111 (1998).
Murphy, S. K. et al. Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelial ovarian cancer. Mol. Cancer Res. 4, 283–292 (2006).
Uyeno, S. et al. IGF2 but not H19 shows loss of imprinting in human glioma. Cancer Res. 56, 5356–5359 (1996).
Yuan, J. et al. Aberrant methylation and silencing of ARHI, an imprinted tumor suppressor gene in which the function is lost in breast cancers. Cancer Res 63, 4174–4180 (2003).
Astuti, D. et al. Epigenetic alteration at the DLK1–GTL2 imprinted domain in human neoplasia: analysis of neuroblastoma, phaeochromocytoma and Wilms' tumour. Br. J. Cancer 92, 1574–1580 (2005).
Pedersen, I. S. et al. Frequent loss of imprinting of PEG1/MEST in invasive breast cancer. Cancer Res 59, 5449–5451 (1999).
Varambally, S., et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419, 624–629 (2002).
Fraga, M. F. et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nature Genet. 37, 391–400 (2005).
Tamaru, H. & Selker, E. U. A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414, 277–283 (2001).
Terranova, R., Agherbi, H., Boned, A., Meresse, S. & Djabali, M. Histone and DNA methylation defects at Hox genes in mice expressing a SET domain-truncated form of Mll. Proc. Natl Acad. Sci. USA 103, 6629–6634 (2006).
Esteve, P. O. et al. Direct interaction between DNMT1and G9a coordinates DNA and histone methylation during replication. Genes Dev. 20, 3089–3103 (2006).
Rozenblatt-Rosen, O. et al. The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components of the SWI/SNF complex. Proc. Natl Acad. Sci. USA 95, 4152–4157 (1998).
Versteege, I. et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394, 203–206 (1998).
Kurotaki, N. et al. Haploinsufficiency of NSD1 causes Sotos syndrome. Nature Genet. 30, 365–366 (2002).
Scott, M. R., Westphal, K. H. & Rigby, P. W. Activation of mouse genes in transformed cells. Cell 34, 557–567 (1983).
Veigl, M. L. et al. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc. Natl Acad. Sci. USA 95, 8698–8702 (1998).
Bachman, K. E. et al. Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene. Cancer Cell 3, 89–95 (2003).
DeBaun, M. R. & Tucker, M. A. Risk of cancer during the first four years of life in children from the Beckwith–Wiedemann syndrome registry. J. Pediatr. 132, 398–400 (1998).
Cui, H., Horon, I. L., Ohlsson, R., Hamilton, S. R. & Feinberg, A. P. Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability. Nature Med. 4, 1276–1280 (1998).
Cui, H. et al. Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 299, 1753–1755 (2003).
Woodson, K. et al. Loss of insulin-like growth factor-II imprinting and the presence of screen-detected colorectal adenomas in women. J. Natl Cancer Inst. 96, 407–410 (2004).
Toyota, M. et al. CpG island methylator phenotype in colorectal cancer. Proc. Natl Acad. Sci. USA 96, 8681–8686 (1999).
Holst, C. R. et al. Methylation of p16INK4a promoters occurs in vivo in histologically normal human mammary epithelia. Cancer Res. 63, 1596–1601 (2003).
Yamada, Y. et al. Opposing effects of DNA hypomethylation on intestinal and liver carcinogenesis. Proc. Natl Acad. Sci. USA 102, 13580–13585 (2005).
Gaudet, F. et al. Induction of tumors in mice by genomic hypomethylation. Science 300, 489–492 (2003).
Eden, A., Gaudet, F., Waghmare, A. & Jaenisch, R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300, 455 (2003).
Laird, P. W. et al. Suppression of intestinal neoplasia by DNA hypomethylation. Cell 81, 197–205 (1995).
Chen, W. Y. et al. Heterozygous disruption of Hic1 predisposes mice to a gender-dependent spectrum of malignant tumors. Nature Genet. 33, 197–202 (2003).
Sakatani, T. et al. Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice. Science 307, 1976–1978 (2005).
Holm, T. M. et al. Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer Cell 8, 275–285 (2005).
Feinberg, A. P., Ohlsson, R. & Henikoff, S. The epigenetic progenitor origin of human cancer. Nature Rev. Genet. 7, 21–33 (2006).
Harper, J. et al. Soluble IGF2 receptor rescues ApcMin/+ intestinal adenoma progression induced by Igf2 loss of imprinting. Cancer Res. 66, 1940–1948 (2006).
Ravenel, J.D. et al. Loss of imprinting of insulin-like growth factor-II (IGF2) gene in distinguishing specific biologic subtypes of Wilms tumor. J. Natl Cancer Inst. 93, 1698–1703 (2001).
Hochedlinger, K. et al. Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev. 18, 1875–1885 (2004).
Hu, M. et al. Distinct epigenetic changes in the stromal cells of breast cancers. Nature Genet. 37, 899–905 (2005).
Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006).
Horton, S. J. et al. Continuous MLL–ENL expression is necessary to establish a 'Hox Code' and maintain immortalization of hematopoietic progenitor cells. Cancer Res. 65, 9245–9252 (2005).
Krivtsov, A. V. et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 442, 818–822 (2006).
Boyer, L. A. et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441, 349–353 (2006).
Skuse, D. H. et al. Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function. Nature 387, 705–708 (1997).
Raefski, A. S. & O'Neill, M. J. Identification of a cluster of X-linked imprinted genes in mice. Nature Genet. 37, 620–624 (2005).
Bailey, A. et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol. Med. 25, 63–77 (1995).
Kates, W. R. et al. Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype for autism. Am. J. Psychiatry 161, 539–546 (2004).
Kato, T., Iwamoto, K., Kakiuchi, C., Kuratomi, G. & Okazaki, Y. Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders. Mol. Psychiatry 10, 622–630 (2005).
International Molecular Genetic Study of Autism Consortium. Further characterization of the autism susceptibility locus AUTS1 on chromosome 7q. Hum. Mol. Genet. 10, 973–982 (2001).
McInnis, M. G. et al. Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12. Mol. Psychiatry 8, 288–298 (2003).
Lu, Q. et al. Epigenetics, disease, and therapeutic interventions. Ageing Res. Rev. 5, 449–467 (2006).
Quddus, J. et al. Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice. J. Clin. Invest. 92, 38–53 (1993).
Richardson, B. DNA methylation and autoimmune disease. Clin. Immunol. 109, 72–79 (2003).
Sutherland, J. E. & Costa, M. Epigenetics and the environment. Ann. NY Acad. Sci. 983, 151–160 (2003).
Anway, M. D., Cupp, A. S., Uzumcu, M. & Skinner, M. K. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308, 1466–1469 (2005).
Waterland, R. A., Lin, J. R., Smith, C. A. & Jirtle, R. L. Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum. Mol. Genet. 15, 705–716 (2006).
Waterland, R. A. & Jirtle, R. L. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol. Cell. Biol. 23, 5293–5300 (2003).
Giovannucci, E. Alcohol, one-carbon metabolism, and colorectal cancer: recent insights from molecular studies. J. Nutr. 134, 2475S–2481S (2004).
Weaver, I. C. et al. Epigenetic programming by maternal behavior. Nature Neurosci. 7, 847–854 (2004).
DeBaun, M. R., Niemitz, E. L. & Feinberg, A. P. Association of in vitro fertilization with Beckwith–Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am. J. Hum. Genet. 72, 156–160 (2003).
Niemitz, E. L. & Feinberg, A. P. Epigenetics and assisted reproductive technology: a call for investigation. Am. J. Hum. Genet. 74, 599–609 (2004).
Bjornsson, H. T., Fallin, M. D. & Feinberg, A. P. An integrated epigenetic and genetic approach to common human disease. Trends Genet. 20, 350–358 (2004).
Fraga, M. F. et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc. Natl Acad. Sci. USA 102, 10604–10609 (2005).
Rutherford, S. L. & Lindquist, S. Hsp90 as a capacitor for morphological evolution. Nature 396, 336–342 (1998).
Sollars, V. et al. Evidence for an epigenetic mechanism by which Hsp90 acts as a capacitor for morphological evolution. Nature Genet. 33, 70–74 (2003).
Lehner, B., Crombie, C., Tischler, J., Fortunato, A. & Fraser, A. G. Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways. Nature Genet. 38, 896–903 (2006).
Callinan, P. A. & Feinberg, A. P. The emerging science of epigenomics. Hum. Mol. Genet. 15, R95–R101 (2006).
Mack, G. S. Epigenetic cancer therapy makes headway. J. Natl Cancer Inst. 98, 1443–1444 (2006).
Yee, K. W., Jabbour, E., Kantarjian, H. M. & Giles, F. J. Clinical experience with decitabine in North American patients with myelodysplastic syndrome. Ann. Hematol. 84 (suppl. 13), 18–24 (2005).
Zheng, Y. et al. Selective HAT inhibitors as mechanistic tools for protein acetylation. Methods Enzymol. 376, 188–199 (2004).
Iyer, N. G., Ozdag, H. & Caldas, C. p300/CBP and cancer. Oncogene 23, 4225–4231 (2004).
Phiel, C. J. et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J. Biol. Chem. 276, 36734–36741 (2001).