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PMID: 19308066 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Linking DNA methylation and histone modification: patterns and paradigms.

Nature reviews. Genetics ·Vol. 10 ·No. 5 ·2009-05-00 ·Pages 295-304

Cedar H, Bergman Y

Abstract

Both DNA methylation and histone modification are involved in establishing patterns of gene repression during development. Certain forms of histone methylation cause local formation of heterochromatin, which is readily reversible, whereas DNA methylation leads to stable long-term repression. It has recently become apparent that DNA methylation and histone modification pathways can be dependent on one another, and that this crosstalk can be mediated by biochemical interactions between SET domain histone methyltransferases and DNA methyltransferases. Relationships between DNA methylation and histone modification have implications for understanding normal development as well as somatic cell reprogramming and tumorigenesis.

MeSH Terms
Animals DNA/metabolism DNA Methylation DNA-Cytosine Methylases/metabolism Heterochromatin/metabolism Histone Methyltransferases Histone-Lysine N-Methyltransferase/metabolism Histones/metabolism Humans Models, Biological Neoplasms/metabolism
Chemicals
Heterochromatin Histones DNA DNA-Cytosine Methylases Histone Methyltransferases Histone-Lysine N-Methyltransferase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Cedar Howard
Department of Developmental Biology and Cancer Research, Hebrew University Medical School, Ein Kerem, Jerusalem 91120, Israel. cedar@cc.huji.ac.il
Bergman Yehudit
References (105)
105 references, click to expand
  1. Mechanisms involved in the regulation of histone lysine demethylases.
    Curr Opin Cell Biol. 2008 Jun;20(3):316-25 PMID: 18440794
  2. Demethylation of CpG islands in embryonic cells.
    Nature. 1991 May 16;351(6323):239-41 PMID: 2041571
  3. Dicer is essential for formation of the heterochromatin structure in vertebrate cells.
    Nat Cell Biol. 2004 Aug;6(8):784-91 PMID: 15247924
  4. DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity.
    EMBO J. 2008 Oct 22;27(20):2691-701 PMID: 18818693
  5. The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin.
    Science. 2008 Dec 12;322(5908):1717-20 PMID: 18988810
  6. Functional cooperation between HP1 and DNMT1 mediates gene silencing.
    Genes Dev. 2007 May 15;21(10):1169-78 PMID: 17470536
  7. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation.
    Nature. 2007 Feb 8;445(7128):671-5 PMID: 17268471
  8. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA.
    Nature. 2007 Dec 6;450(7171):908-12 PMID: 17994007
  9. DNA methylation represses transcription in vivo.
    Nat Genet. 1999 Jun;22(2):203-6 PMID: 10369268
  10. DNA demethylation in vitro: involvement of RNA.
    Cell. 1996 Sep 6;86(5):709-18 PMID: 8797818
  11. Delayed de novo methylation in teratocarcinoma suggests additional tissue-specific mechanisms for controlling gene expression.
    Nature. 1983 Jan 6;301(5895):32-7 PMID: 6296681
  12. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development.
    Development. 1987 Mar;99(3):371-82 PMID: 3653008
  13. Frequent derepression of G6PD and HPRT on the marsupial inactive X chromosome associated with cell proliferation in vitro.
    Exp Cell Res. 1989 Jun;182(2):597-609 PMID: 2721594
  14. Sp1 elements protect a CpG island from de novo methylation.
    Nature. 1994 Sep 29;371(6496):435-8 PMID: 8090226
  15. Evidence for an instructive mechanism of de novo methylation in cancer cells.
    Nat Genet. 2006 Feb;38(2):149-53 PMID: 16444255
  16. Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island.
    Genes Dev. 1994 Oct 1;8(19):2282-92 PMID: 7958895
  17. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex.
    Nature. 1998 May 28;393(6683):386-9 PMID: 9620804
  18. PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing.
    Nat Struct Mol Biol. 2009 Mar;16(3):304-311 PMID: 19234465
  19. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds.
    Cell Stem Cell. 2008 Nov 6;3(5):568-74 PMID: 18983970
  20. X chromosome dosage compensation: how mammals keep the balance.
    Annu Rev Genet. 2008;42:733-72 PMID: 18729722
  21. Targeted inhibition of V(D)J recombination by a histone methyltransferase.
    Nat Immunol. 2004 Mar;5(3):309-16 PMID: 14985714
  22. Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells.
    Cell Stem Cell. 2007 Sep 13;1(3):299-312 PMID: 18371364
  23. Dynamics of demethylation and activation of the alpha-actin gene in myoblasts.
    Cell. 1990 Dec 21;63(6):1229-37 PMID: 2261641
  24. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
    Cell. 2006 Aug 25;126(4):663-76 PMID: 16904174
  25. The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase.
    Nucleic Acids Res. 2003 May 1;31(9):2305-12 PMID: 12711675
  26. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA.
    Nature. 2007 Aug 9;448(7154):714-7 PMID: 17687327
  27. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells.
    J Biol Chem. 2006 Jul 14;281(28):19489-500 PMID: 16682412
  28. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells.
    Nat Genet. 2005 Aug;37(8):853-62 PMID: 16007088
  29. Polycomb and polyhomeotic are constituents of a multimeric protein complex in chromatin of Drosophila melanogaster.
    EMBO J. 1992 Aug;11(8):2941-50 PMID: 1353445
  30. A histone H3 methyltransferase controls DNA methylation in Neurospora crassa.
    Nature. 2001 Nov 15;414(6861):277-83 PMID: 11713521
  31. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription.
    Nat Genet. 1998 Jun;19(2):187-91 PMID: 9620779
  32. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation.
    Nature. 2007 Sep 13;449(7159):248-51 PMID: 17713477
  33. DNA methylation and complete transcriptional silencing of cancer genes persist after depletion of EZH2.
    Cancer Res. 2007 Jun 1;67(11):5097-102 PMID: 17545586
  34. The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes.
    Science. 1995 Mar 3;267(5202):1360-3 PMID: 7871435
  35. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state.
    Nature. 2007 Jul 19;448(7151):318-24 PMID: 17554336
  36. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin.
    Curr Biol. 2003 Jul 15;13(14):1192-200 PMID: 12867029
  37. Developmental progression of Gpd expression from the inactive X chromosome of the Virginia opossum.
    Dev Genet. 1995;16(4):367-78 PMID: 7641417
  38. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes.
    Nat Struct Mol Biol. 2008 Nov;15(11):1176-1183 PMID: 18953337
  39. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution.
    Cell Stem Cell. 2007 Jun 7;1(1):55-70 PMID: 18371336
  40. Genome-scale DNA methylation maps of pluripotent and differentiated cells.
    Nature. 2008 Aug 7;454(7205):766-70 PMID: 18600261
  41. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation.
    Mol Cell. 2008 Oct 24;32(2):232-46 PMID: 18951091
  42. Control of developmental regulators by Polycomb in human embryonic stem cells.
    Cell. 2006 Apr 21;125(2):301-13 PMID: 16630818
  43. Methylation of the Hprt gene on the inactive X occurs after chromosome inactivation.
    Cell. 1987 Jan 16;48(1):39-46 PMID: 3791414
  44. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells.
    Nature. 2007 Aug 2;448(7153):553-60 PMID: 17603471
  45. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase.
    Nature. 2002 Apr 4;416(6880):556-60 PMID: 11898023
  46. A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases.
    Nat Struct Mol Biol. 2008 Mar;15(3):268-79 PMID: 18311151
  47. The role of DNA methylation in setting up chromatin structure during development.
    Nat Genet. 2003 Jun;34(2):187-92 PMID: 12740577
  48. Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication.
    Genes Dev. 2006 Nov 15;20(22):3089-103 PMID: 17085482
  49. Possible involvement of the RNAi pathway in trinucleotide repeat expansion diseases.
    J Biomol Struct Dyn. 2005 Dec;23(3):233-5 PMID: 16218750
  50. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing.
    Nat Genet. 2007 Feb;39(2):237-42 PMID: 17211412
  51. The interaction of the SRA domain of ICBP90 with a novel domain of DNMT1 is involved in the regulation of VEGF gene expression.
    Oncogene. 2008 Apr 3;27(15):2187-97 PMID: 17934516
  52. Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line.
    Genes Dev. 1992 May;6(5):705-14 PMID: 1577268
  53. The polycomb group protein EZH2 is involved in progression of prostate cancer.
    Nature. 2002 Oct 10;419(6907):624-9 PMID: 12374981
  54. Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors.
    Mol Cell. 2008 Jun 20;30(6):755-66 PMID: 18514006
  55. A bivalent chromatin structure marks key developmental genes in embryonic stem cells.
    Cell. 2006 Apr 21;125(2):315-26 PMID: 16630819
  56. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.
    Cell. 1999 Oct 29;99(3):247-57 PMID: 10555141
  57. G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription.
    EMBO J. 2008 Oct 22;27(20):2681-90 PMID: 18818694
  58. Properties and localization of DNA methyltransferase in preimplantation mouse embryos: implications for genomic imprinting.
    Genes Dev. 1992 Dec;6(12B):2536-41 PMID: 1340468
  59. Mouse germline restriction of Oct4 expression by germ cell nuclear factor.
    Dev Cell. 2001 Sep;1(3):377-87 PMID: 11702949
  60. Abnormal regulation of DNA methyltransferase expression during colorectal carcinogenesis.
    Cancer Res. 1999 Aug 15;59(16):3855-60 PMID: 10463569
  61. The emerging functions of histone demethylases.
    Curr Opin Genet Dev. 2008 Apr;18(2):159-68 PMID: 18281209
  62. The Polycomb group protein EZH2 directly controls DNA methylation.
    Nature. 2006 Feb 16;439(7078):871-4 PMID: 16357870
  63. The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation.
    Nat Genet. 2009 Jan;41(1):125-9 PMID: 19098913
  64. The epigenomics of cancer.
    Cell. 2007 Feb 23;128(4):683-92 PMID: 17320506
  65. Regulation of the Oct-4 gene by nuclear receptors.
    Nucleic Acids Res. 1994 Mar 25;22(6):901-11 PMID: 8152920
  66. A chromatin landmark and transcription initiation at most promoters in human cells.
    Cell. 2007 Jul 13;130(1):77-88 PMID: 17632057
  67. Epigenetic ontogeny of the Igk locus during B cell development.
    Nat Immunol. 2005 Feb;6(2):198-203 PMID: 15619624
  68. MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells.
    Nat Struct Mol Biol. 2008 Mar;15(3):259-67 PMID: 18311153
  69. High-resolution profiling of histone methylations in the human genome.
    Cell. 2007 May 18;129(4):823-37 PMID: 17512414
  70. A combined chemical and genetic approach for the generation of induced pluripotent stem cells.
    Cell Stem Cell. 2008 Jun 5;2(6):525-8 PMID: 18522845
  71. TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation.
    Mol Cell. 2009 Feb 13;33(3):344-53 PMID: 19217408
  72. Whole-genome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells.
    Cell Stem Cell. 2007 Sep 13;1(3):286-98 PMID: 18371363
  73. The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors.
    Nucleic Acids Res. 1999 Jun 1;27(11):2291-8 PMID: 10325416
  74. HP1 is essential for DNA methylation in neurospora.
    Mol Cell. 2004 Feb 13;13(3):427-34 PMID: 14967149
  75. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei.
    Cell. 1992 Nov 27;71(5):865-73 PMID: 1423634
  76. G9a and Jhdm2a regulate embryonic stem cell fusion-induced reprogramming of adult neural stem cells.
    Stem Cells. 2008 Aug;26(8):2131-41 PMID: 18535151
  77. Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks.
    Nature. 2008 Nov 6;456(7218):125-9 PMID: 18815594
  78. Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis.
    Science. 2009 Feb 20;323(5917):1074-7 PMID: 19119186
  79. RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production.
    Proc Natl Acad Sci U S A. 2005 Jan 4;102(1):152-7 PMID: 15615848
  80. DNA methylation dictates histone H3K4 methylation.
    Mol Cell Biol. 2007 Apr;27(7):2746-57 PMID: 17242185
  81. Role of DNA methylation in stable gene repression.
    J Biol Chem. 2007 Apr 20;282(16):12194-200 PMID: 17311920
  82. The reprogramming language of pluripotency.
    Curr Opin Genet Dev. 2008 Apr;18(2):123-9 PMID: 18356040
  83. Stem cell regulation by polycomb repressors: postponing commitment.
    Curr Opin Cell Biol. 2008 Apr;20(2):201-7 PMID: 18291635
  84. Epigenetic stem cell signature in cancer.
    Nat Genet. 2007 Feb;39(2):157-8 PMID: 17200673
  85. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells.
    Genes Dev. 2007 Oct 15;21(20):2545-57 PMID: 17938240
  86. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis.
    Nat Cell Biol. 2006 Feb;8(2):188-94 PMID: 16415856
  87. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome.
    Science. 2008 Oct 31;322(5902):750-6 PMID: 18974356
  88. Methylation of HoxA5 and HoxB5 and its relevance to expression during mouse development.
    Gene. 2003 Jan 2;302(1-2):65-72 PMID: 12527197
  89. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome.
    Nat Genet. 2007 Apr;39(4):457-66 PMID: 17334365
  90. Polycomb complexes repress developmental regulators in murine embryonic stem cells.
    Nature. 2006 May 18;441(7091):349-53 PMID: 16625203
  91. A unique developmental pattern of Oct-3/4 DNA methylation is controlled by a cis-demodification element.
    J Biol Chem. 2002 Sep 13;277(37):34521-30 PMID: 12110668
  92. DNA methylation landscapes: provocative insights from epigenomics.
    Nat Rev Genet. 2008 Jun;9(6):465-76 PMID: 18463664
  93. Silence of the genes--mechanisms of long-term repression.
    Nat Rev Genet. 2005 Aug;6(8):648-54 PMID: 16012529
  94. A dynamic balance between ARP-1/COUP-TFII, EAR-3/COUP-TFI, and retinoic acid receptor:retinoid X receptor heterodimers regulates Oct-3/4 expression in embryonal carcinoma cells.
    Mol Cell Biol. 1995 Feb;15(2):1034-48 PMID: 7823919
  95. DNA methylation models histone acetylation.
    Nature. 1998 Aug 27;394(6696):842 PMID: 9732866
  96. Dnmt3L and the establishment of maternal genomic imprints.
    Science. 2001 Dec 21;294(5551):2536-9 PMID: 11719692
  97. Polycomb complexes and epigenetic states.
    Curr Opin Cell Biol. 2008 Jun;20(3):266-73 PMID: 18439810
  98. Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line.
    Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12979-84 PMID: 18753622
  99. UHRF1 plays a role in maintaining DNA methylation in mammalian cells.
    Science. 2007 Sep 21;317(5845):1760-4 PMID: 17673620
  100. Dissecting direct reprogramming through integrative genomic analysis.
    Nature. 2008 Jul 3;454(7200):49-55 PMID: 18509334
  101. Genomic patterns of DNA methylation: targets and function of an epigenetic mark.
    Curr Opin Cell Biol. 2007 Jun;19(3):273-80 PMID: 17466503
  102. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer.
    Science. 2008 Dec 12;322(5908):1695-9 PMID: 19008416
  103. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing.
    Genes Dev. 2005 Feb 15;19(4):489-501 PMID: 15713842
  104. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45.
    Cell. 2008 Dec 26;135(7):1201-12 PMID: 19109892
  105. Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus.
    PLoS Genet. 2008 Aug 01;4(8):e1000145 PMID: 18670629
Article Info
Journal
Nature reviews. Genetics
Abbr.
Nat Rev Genet
ISSN
1471-0064
DOI
10.1038/nrg2540
Email
cedar@cc.huji.ac.il
Published
2009-05-00
Pages
295-304
Language
English
Region
England
NLM ID
100962779
Subset
IM
External Links
PubMed source DOI: 10.1038/nrg2540 View journal details
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