Functions of DNA methylation: islands, start sites, gene bodies and beyond

Nature Reviews Genetics - Tập 13 Số 7 - Trang 484-492 - 2012
Peter A. Jones1
1USC Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, Los Angeles, California 90089-99176, USA. [email protected]

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Holliday, R. & Pugh, J. E. DNA modification mechanisms and gene activity during development. Science 187, 226–232 (1975).

Riggs, A. D. X inactivation, differentiation, and DNA methylation. Cytogenet. Cell Genet. 14, 9–25 (1975).

Cokus, S. J. et al. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452, 215–219 (2008). This was the first paper to provide single-base resolution of DNA methylation genome-wide.

Rountree, M. R. & Selker, E. U. DNA methylation inhibits elongation but not initiation of transcription in Neurospora crassa. Genes Dev. 11, 2383–2395 (1997).

Lister, R. et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462, 315–322 (2009). This was the first report of a human methylome at single-base resolution.

Smallwood, S. A. et al. Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nature Genet. 43, 811–814 (2011).

Illingworth, R. S. & Bird, A. P. CpG islands—'a rough guide'. FEBS Lett. 583, 1713–1720 (2009).

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).

Moarefi, A. H. & Chedin, F. ICF syndrome mutations cause a broad spectrum of biochemical defects in DNMT3B-mediated de novo DNA methylation. J. Mol. Biol. 409, 758–772 (2011).

Jones, P. A. & Liang, G. Rethinking how DNA methylation patterns are maintained. Nature Rev. Genet. 10, 805–811 (2009).

Bhutani, N. et al. Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 463, 1042–1047 (2010).

Ooi, S. K. et al. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448, 714–717 (2007). This paper provided a structural basis to the mechanisms of de novo methylation and showed how active histone marks could exclude methylation of DNA.

Li, E., Bestor, T. H. & Jaenisch, R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915–926 (1992).

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). This was a key paper in defining the need for DNA cytosine methylation in mammals.

Jackson-Grusby, L. et al. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nature Genet. 27, 31–39 (2001).

Chen, T. et al. Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells. Nature Genet. 39, 391–396 (2007).

Tsumura, A. et al. Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Genes Cells 11, 805–814 (2006).

Challen, G. A. et al. Dnmt3a is essential for hematopoietic stem cell differentiation. Nature Genet. 44, 23–31 (2011).

Ooi, S. K. & Bestor, T. H. The colorful history of active DNA demethylation. Cell 133, 1145–1148 (2008).

Wu, H. & Zhang, Y. Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. Genes Dev. 25, 2436–2452 (2011).

Branco, M. R., Ficz, G. & Reik, W. Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nature Rev. Genet. 13, 7–13 (2012).

Popp, C. et al. Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature 463, 1101–1105 (2010).

Inoue, A. & Zhang, Y. Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science 334, 194 (2011).

Iqbal, K., Jin, S. G., Pfeifer, G. P. & Szabo, P. E. Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc. Natl Acad. Sci. USA 108, 3642–3647 (2011).

Cortellino, S. et al. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell 146, 67–79 (2011).

Cortazar, D. et al. Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability. Nature 470, 419–423 (2011).

Gu, T. P. et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477, 606–610 (2011).

Wossidlo, M. et al. 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nature Commun. 2, 241 (2011).

Baylin, S. B. & Jones, P. A. A decade of exploring the cancer epigenome — biological and translational implications. Nature Rev. Cancer 11, 726–734 (2011).

Kelly, T. K. et al. H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes. Mol. Cell 39, 901–911 (2010).

Gal-Yam, E. N. et al. Constitutive nucleosome depletion and ordered factor assembly at the GRP78 promoter revealed by single molecule footprinting. PLoS Genet. 2, e160 (2006).

Taberlay, P. C. et al. Polycomb-repressed genes have permissive enhancers that initiate reprogramming. Cell 147, 1283–1294 (2011).

Farthing, C. R. et al. Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes. PLoS Genet. 4, e1000116 (2008).

Han, H. et al. DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter. Hum. Mol. Genet. 20, 4299–4310 (2011).

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).

Gal-Yam, E. N. et al. Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line. Proc. Natl Acad. Sci. USA 105, 12979–12984 (2008).

Hashimshony, T., Zhang, J., Keshet, I., Bustin, M. & Cedar, H. The role of DNA methylation in setting up chromatin structure during development. Nature Genet. 34, 187–192 (2003).

Kass, S. U., Landsberger, N. & Wolffe, A. P. DNA methylation directs a time-dependent repression of transcription initiation. Curr. Biol. 7, 157–165 (1997).

Venolia, L. & Gartler, S. M. Comparison of transformation efficiency of human active and inactive X-chromosomal DNA. Nature 302, 82–83 (1983). This is a key paper that unequivocally established that the covalent application of methyl groups to DNA could result in silencing and is involved in X-chromosome inactivation.

Lock, L. F., Takagi, N. & Martin, G. R. Methylation of the Hprt gene on the inactive X occurs after chromosome inactivation. Cell 48, 39–46 (1987). This paper unexpectedly showed that methylation of cytosine was not the primary silencing mechanism for X inactivation.

Ohm, J. E. et al. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nature Genet. 39, 237–242 (2007).

Schlesinger, Y. et al. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nature Genet. 39, 232–236 (2007).

Widschwendter, M. et al. Epigenetic stem cell signature in cancer. Nature Genet. 39, 157–158 (2007).

Irizarry, R. A. et al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nature Genet. 41, 178–186 (2009).

You, J. S. et al. OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genes. Proc. Natl Acad. Sci. USA 108, 14497–14502 (2011).

Zilberman, D., Coleman-Derr, D., Ballinger, T. & Henikoff, S. Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks. Nature 456, 125–129 (2008). This paper showed the importance of histone variants in relation to DNA methylation. Previously, most of the focus was on histone modification.

Conerly, M. L. et al. Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis. Genome Res. 20, 1383–1390 (2010).

Thomson, J. P. et al. CpG islands influence chromatin structure via the CpG-binding protein Cfp1. Nature 464, 1082–1086 (2010).

Williams, K., Christensen, J. & Helin, K. DNA methylation: TET proteins—guardians of CpG islands? EMBO Rep. 13, 28–35 (2011).

Jones, P. A. et al. De novo methylation of the MyoD1 CpG island during the establishment of immortal cell lines. Proc. Natl Acad. Sci. USA 87, 6117–6121 (1990).

Hitchins, M. P. et al. Dominantly inherited constitutional epigenetic silencing of MLH1 in a cancer-affected family is linked to a single nucleotide variant within the 5′UTR. Cancer Cell 20, 200–213 (2011). This study demonstrated that single-nucleotide variants that decrease promoter activity can lead to preferential allele-specific methylation.

Boumber, Y. A. et al. An Sp1/Sp3 binding polymorphism confers methylation protection. PLoS Genet. 4, e1000162 (2008).

Rideout, W. M., I. I. I., Coetzee, G. A., Olumi, A. F. & Jones, P. A. 5-Methylcytosine as an endogenous mutagen in the human LDL receptor and p53 genes. Science 249, 1288–1290 (1990).

Jones, P. A. The DNA methylation paradox. Trends Genet. 15, 34–37 (1999).

Illingworth, R. S. et al. Orphan CpG islands identify numerous conserved promoters in the mammalian genome. PLoS Genet. 6, e1001134 (2010).

Wolf, S. F., Jolly, D. J., Lunnen, K. D., Friedmann, T. & Migeon, B. R. Methylation of the hypoxanthine phosphoribosyltransferase locus on the human X chromosome: implications for X-chromosome inactivation. Proc. Natl Acad. Sci. USA 81, 2806–2810 (1984).

Hellman, A. & Chess, A. Gene body-specific methylation on the active X chromosome. Science 315, 1141–1143 (2007).

Feng, S. et al. Conservation and divergence of methylation patterning in plants and animals. Proc. Natl Acad. Sci. USA 107, 8689–8694 (2010).

Larsen, F., Solheim, J. & Prydz, H. A methylated CpG island 3′ in the apolipoprotein-E gene does not repress its transcription. Hum. Mol. Genet. 2, 775–780 (1993).

Maunakea, A. K. et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 466, 253–257 (2010).

Nguyen, C. et al. Susceptibility of nonpromoter CpG islands to de novo methylation in normal and neoplastic cells. J. Natl Cancer Inst. 93, 1465–1472 (2001).

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).

Yoder, J. A., Walsh, C. P. & Bestor, T. H. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 13, 335–340 (1997). This paper pointed out the crucial role of 5mC in suppressing the transcription of transposable elements.

Hahn, M. A., Wu, X., Li, A. X., Hahn, T. & Pfeifer, G. P. Relationship between gene body DNA methylation and intragenic H3K9me3 and H3K36me3 chromatin marks. PLoS ONE 6, e18844 (2011).

Laurent, L. et al. Dynamic changes in the human methylome during differentiation. Genome Res. 20, 320–331 (2010).

Schwartz, S., Meshorer, E. & Ast, G. Chromatin organization marks exon-intron structure. Nature Struct. Mol. Biol. 16, 990–995 (2009).

Chodavarapu, R. K. et al. Relationship between nucleosome positioning and DNA methylation. Nature 466, 388–392 (2010).

Shukla, S. et al. CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Nature 479, 74–79 (2011).

Lister, R. et al. Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell 133, 523–536 (2008).

Stadler, M. B. et al. DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature 480, 490–495 (2011).

Schmidl, C. et al. Lineage-specific DNA methylation in T cells correlates with histone methylation and enhancer activity. Genome Res. 19, 1165–1174 (2009).

Wiench, M. et al. DNA methylation status predicts cell type-specific enhancer activity. EMBO J. 30, 3028–3039 (2011).

Saluz, H. P., Jiricny, J. & Jost, J. P. Genomic sequencing reveals a positive correlation between the kinetics of strand-specific DNA demethylation of the overlapping estradiol/glucocorticoid-receptor binding sites and the rate of avian vitellogenin mRNA synthesis. Proc. Natl Acad. Sci. USA 83, 7167–7171 (1986).

Stroud, H., Feng, S., Morey Kinney, S., Pradhan, S. & Jacobsen, S. E. 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells. Genome Biol. 12, R54 (2011).

Szulwach, K. E. et al. Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. PLoS Genet. 7, e1002154 (2011).

Williams, K. et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473, 343–348 (2011).

Ficz, G. et al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473, 398–402 (2011).

Wu, S. C. & Zhang, Y. Active DNA demethylation: many roads lead to Rome. Nature Rev. Mol. Cell. Biol. 11, 607–620 (2010).

Bell, A. C. & Felsenfeld, G. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405, 482–485 (2000). This was a key paper showing how methylation of CTCF sites could alter insulator function by directly blocking binding of CTCF.

Takai, D., Gonzales, F. A., Tsai, Y. C., Thayer, M. J. & Jones, P. A. Large scale mapping of methylcytosines in CTCF-binding sites in the human H19 promoter and aberrant hypomethylation in human bladder cancer. Hum. Mol. Genet. 10, 2619–2626 (2001).

Lin, J. C. et al. Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island. Cancer Cell 12, 432–444 (2007).

Wade, P. A. & Wolffe, A. P. ReCoGnizing methylated DNA. Nature Struct. Biol. 8, 575–577 (2001).

Hsieh, C. L. Dynamics of DNA methylation pattern. Curr. Opin. Genet. Dev. 10, 224–228 (2000).

Prendergast, G. C. & Ziff, E. B. Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. Science 251, 186–189 (1991).

Harrington, M. A., Jones, P. A., Imagawa, M. & Karin, M. Cytosine methylation does not affect binding of transcription factor Sp1. Proc. Natl Acad. Sci. USA 85, 2066–2070 (1988).

Simonsson, S. & Gurdon, J. DNA demethylation is necessary for the epigenetic reprogramming of somatic cell nuclei. Nature Cell Biol. 6, 984–990 (2004).

Chen, P. Y., Feng, S., Joo, J. W., Jacobsen, S. E. & Pellegrini, M. A comparative analysis of DNA methylation across human embryonic stem cell lines. Genome Biol. 12, R62 (2011).

American Association for Cancer Research Human Epigenome Task Force & European Union, Network of Excellence & Scientific Advisory Board. Moving AHEAD with an international human epigenome project. Nature 454, 711–715 (2008).

Harris, R. A. et al. Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications. Nature Biotech. 28, 1097–1105 (2010). This is a good criticial review of sequencing-based methods for studying 5mC patterns.

Huang, Y. et al. The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing. PLoS ONE 5, e8888 (2010).

Cooper, D. N. & Youssoufian, H. The CpG dinucleotide and human genetic disease. Hum. Genet. 78, 151–155 (1988). This paper clearly highlighted the important role of 5mC in generating disease-causing mutations.

The Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 474, 609–615 (2011).

Stirzaker, C. et al. Extensive DNA methylation spanning the Rb promoter in retinoblastoma tumors. Cancer Res. 57, 2229–2237 (1997).

Markl, I. D. et al. Global and gene-specific epigenetic patterns in human bladder cancer genomes are relatively stable in vivo and in vitro over time. Cancer Res. 61, 5875–5884 (2001).

Ley, T. J. et al. DNMT3A mutations in acute myeloid leukemia. N. Engl. J. Med. 363, 2424–2433 (2010).

Figueroa, M. E. et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18, 553–567 (2010).

Bell, M. V. et al. Physical mapping across the fragile X: hypermethylation and clinical expression of the fragile X syndrome. Cell 64, 861–866 (1991).

Xu, G. L. et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402, 187–191 (1999).

Sharma, S., De Carvalho, D. D., Jeong, S., Jones, P. A. & Liang, G. Nucleosomes containing methylated DNA stabilize DNA methyltransferases 3A/3B and ensure faithful epigenetic inheritance. PLoS Genet. 7, e1001286 (2011).

Ong, C. T. & Corces, V. G. Enhancer function: new insights into the regulation of tissue-specific gene expression. Nature Rev. Genet. 12, 283–293 (2011).