Programming of DNA methylation patterns.

DNA methylation represents a form of genome annotation that mediates gene repression by serving as a maintainable mark that can be used to reconstruct silent chromatin following each round of replication. During development, germline DNA methylation is erased in the blastocyst, and a bimodal pattern is established anew at the time of implantation when the entire genome gets methylated while CpG islands are protected. This brings about global repression and allows housekeeping genes to be expressed in all cells of the body. Postimplantation development is characterized by stage- and tissue-specific changes in methylation that ultimately mold the epigenetic patterns that define each individual cell type. This is directed by sequence information in DNA and represents a secondary event that provides long-term expression stability. Abnormal methylation changes play a role in diseases, such as cancer or fragile X syndrome, and may also occur as a function of aging or as a result of environmental influences.

[1]  Chuan He,et al.  Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine , 2011, Science.

[2]  D. Patel,et al.  PHD finger recognition of unmodified histone H3R2 links UHRF1 to regulation of euchromatic gene expression. , 2011, Molecular cell.

[3]  A. Klein-Szanto,et al.  Thymine DNA Glycosylase Is Essential for Active DNA Demethylation by Linked Deamination-Base Excision Repair , 2011, Cell.

[4]  A. Feinberg,et al.  Increased methylation variation in epigenetic domains across cancer types , 2011, Nature Genetics.

[5]  S. Andrews,et al.  Dynamic CpG island methylation landscape in oocytes and preimplantation embryos , 2011, Nature Genetics.

[6]  G. Ming,et al.  Hydroxylation of 5-Methylcytosine by TET1 Promotes Active DNA Demethylation in the Adult Brain , 2011, Cell.

[7]  Keji Zhao,et al.  Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells , 2011, Nature.

[8]  W. Reik,et al.  5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. , 2011, Nature communications.

[9]  D. Patel,et al.  Structure of DNMT1-DNA Complex Reveals a Role for Autoinhibition in Maintenance DNA Methylation , 2011, Science.

[10]  A. Bird,et al.  Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability , 2011, Nature.

[11]  G. Pfeifer,et al.  Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine , 2011, Proceedings of the National Academy of Sciences.

[12]  H. Koseki,et al.  Recruitment of Dnmt1 roles of the SRA protein Np95 (Uhrf1) and other factors. , 2011, Progress in molecular biology and translational science.

[13]  E. Whitelaw,et al.  Transgenerational epigenetic inheritance: more questions than answers. , 2010, Genome research.

[14]  S. Chong,et al.  Tuning in to noise: epigenetics and intangible variation. , 2010, Developmental cell.

[15]  W. Reik,et al.  Epigenetic Reprogramming in Plant and Animal Development , 2010, Science.

[16]  Yi Zhang,et al.  Dnmt3a-Dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic Genes , 2010, Science.

[17]  M. Pellegrini,et al.  Relationship between nucleosome positioning and DNA methylation , 2010, Nature.

[18]  M. Surani,et al.  Genome-Wide Reprogramming in the Mouse Germ Line Entails the Base Excision Repair Pathway , 2010, Science.

[19]  Robert S. Illingworth,et al.  CpG islands influence chromatin structure via the CpG-binding protein Cfp1 , 2010, Nature.

[20]  D. Barlow,et al.  Genomic imprinting mechanisms in embryonic and extraembryonic mouse tissues , 2010, Heredity.

[21]  Chia-Lin Wei,et al.  Dynamic changes in the human methylome during differentiation. , 2010, Genome research.

[22]  Nianxiang Zhang,et al.  Widespread and Tissue Specific Age-related Dna Methylation Material Supplemental Related Content a Hallmark of Cancer Age-dependent Dna Methylation of Genes That Are Suppressed in Stem Cells Is , 2022 .

[23]  M. Pellegrini,et al.  Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency , 2010, Nature.

[24]  P. Fahey,et al.  Maternal Ethanol Consumption Alters the Epigenotype and the Phenotype of Offspring in a Mouse Model , 2010, PLoS genetics.

[25]  Jian Xu,et al.  Transcriptional competence and the active marking of tissue-specific enhancers by defined transcription factors in embryonic and induced pluripotent stem cells. , 2009, Genes & development.

[26]  H. Shibuya,et al.  DNA demethylation in hormone-induced transcriptional derepression , 2009, Nature.

[27]  H. Cedar,et al.  Linking DNA methylation and histone modification: patterns and paradigms , 2009, Nature Reviews Genetics.

[28]  Israel Steinfeld,et al.  Developmental programming of CpG island methylation profiles in the human genome , 2009, Nature Structural &Molecular Biology.

[29]  Shinya Yamanaka,et al.  A Fresh Look at iPS Cells , 2009, Cell.

[30]  Dirk Schübeler,et al.  Methylated DNA immunoprecipitation (MeDIP). , 2009, Methods in molecular biology.

[31]  B. Cairns,et al.  DNA Demethylation in Zebrafish Involves the Coupling of a Deaminase, a Glycosylase, and Gadd45 , 2008, Cell.

[32]  K. Helin,et al.  A model for transmission of the H3K27me3 epigenetic mark , 2008, Nature Cell Biology.

[33]  H. Cedar,et al.  De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes , 2008, Nature Structural &Molecular Biology.

[34]  D. Schübeler,et al.  DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity , 2008, The EMBO journal.

[35]  H. Kimura,et al.  G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription , 2008, The EMBO journal.

[36]  W. Reik,et al.  Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5 , 2008, Nature Cell Biology.

[37]  Gangning Liang,et al.  Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line , 2008, Proceedings of the National Academy of Sciences.

[38]  T. Mikkelsen,et al.  Genome-scale DNA methylation maps of pluripotent and differentiated cells , 2008, Nature.

[39]  Michael B. Stadler,et al.  Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. , 2008, Molecular cell.

[40]  R. Ng,et al.  Epigenetic inheritance of cell differentiation status , 2008, Cell cycle.

[41]  Alun D. Hughes,et al.  The interaction of the SRA domain of ICBP90 with a novel domain of DNMT1 is involved in the regulation of VEGF gene expression , 2008, Oncogene.

[42]  Jim Stalker,et al.  A Novel CpG Island Set Identifies Tissue-Specific Methylation at Developmental Gene Loci , 2008, PLoS biology.

[43]  R. Jaenisch,et al.  Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. , 2007, Genes & development.

[44]  S. Jacobsen,et al.  UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells , 2007, Science.

[45]  H. Scott,et al.  Modifiers of epigenetic reprogramming show paternal effects in the mouse , 2007, Nature Genetics.

[46]  H. Cedar,et al.  Role of DNA Methylation in Stable Gene Repression* , 2007, Journal of Biological Chemistry.

[47]  M. Fraga,et al.  The Polycomb group protein EZH2 directly controls DNA methylation , 2007, Nature.

[48]  Michael B. Stadler,et al.  Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome , 2007, Nature Genetics.

[49]  Christof Niehrs,et al.  Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation , 2007, Nature.

[50]  Zohar Yakhini,et al.  Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer , 2007, Nature Genetics.

[51]  P. Laird,et al.  Epigenetic stem cell signature in cancer , 2007, Nature Genetics.

[52]  Kelly M. McGarvey,et al.  A stem cell–like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing , 2007, Nature Genetics.

[53]  J. D. Engel,et al.  Fine Tuning of Globin Gene Expression by DNA Methylation , 2006, PloS one.

[54]  Guoping Fan,et al.  Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells. , 2006, Human molecular genetics.

[55]  R. Jaenisch,et al.  Dnmt3b Deletion of Suppression of Intestinal Neoplasia By , 2006 .

[56]  A. Bird,et al.  Genomic DNA methylation: the mark and its mediators. , 2006, Trends in biochemical sciences.

[57]  I. Simon,et al.  Evidence for an instructive mechanism of de novo methylation in cancer cells , 2006, Nature Genetics.

[58]  H. Cedar,et al.  G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis , 2006, Nature Cell Biology.

[59]  Stephanie Daignault,et al.  Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer. , 2006, Cancer research.

[60]  Kevin Eggan,et al.  Nuclear Reprogramming of Somatic Cells After Fusion with Human Embryonic Stem Cells , 2005, Science.

[61]  T. Bruxner,et al.  An N-ethyl-N-nitrosourea screen for genes involved in variegation in the mouse. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[62]  B. Oostra,et al.  Molecular dissection of the events leading to inactivation of the FMR1 gene. , 2005, Human molecular genetics.

[63]  R. Jaenisch,et al.  Nuclear cloning, epigenetic reprogramming, and cellular differentiation. , 2004, Cold Spring Harbor symposia on quantitative biology.

[64]  T. Hashimshony,et al.  The role of DNA methylation in setting up chromatin structure during development , 2003, Nature Genetics.

[65]  D. Page,et al.  Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei , 2003, Development.

[66]  Tony Kouzarides,et al.  The Methyl-CpG-binding Protein MeCP2 Links DNA Methylation to Histone Methylation* , 2003, The Journal of Biological Chemistry.

[67]  Colin C. Collins,et al.  Integrated genomic and epigenomic analyses pinpoint biallelic gene inactivation in tumors , 2002, Nature Genetics.

[68]  S. Ceman,et al.  Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile x syndrome. , 2002, American journal of human genetics.

[69]  Y. Bergman,et al.  A Unique Developmental Pattern of Oct-3/4DNA Methylation Is Controlled by a cis-demodification Element* , 2002, The Journal of Biological Chemistry.

[70]  H. Schöler,et al.  Oct4 distribution and level in mouse clones: consequences for pluripotency. , 2002, Genes & development.

[71]  T. Bestor,et al.  Dnmt3L and the Establishment of Maternal Genomic Imprints , 2001, Science.

[72]  M. Groudine,et al.  Genomic Targeting of Methylated DNA: Influence of Methylation on Transcription, Replication, Chromatin Structure, and Histone Acetylation , 2000, Molecular and Cellular Biology.

[73]  G. Felsenfeld,et al.  Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene , 2000, Nature.

[74]  J. Walter,et al.  Embryogenesis: Demethylation of the zygotic paternal genome , 2000, Nature.

[75]  David I. K. Martin,et al.  Epigenetic inheritance at the agouti locus in the mouse , 1999, Nature Genetics.

[76]  D. Haber,et al.  DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development , 1999, Cell.

[77]  I. Simon,et al.  Asynchronous replication of imprinted genes is established in the gametes and maintained during development , 1999, Nature.

[78]  Paul Tempst,et al.  MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex , 1999, Nature Genetics.

[79]  Howard Cedar,et al.  DNA methylation represses transcription in vivo , 1999, Nature Genetics.

[80]  H. Cedar,et al.  Gene expression: The amazing demethylase , 1999, Nature.

[81]  M. Szyf,et al.  A mammalian protein with specific demethylase activity for mCpG DNA , 1999, Nature.

[82]  A. Razin,et al.  The imprinting box of the mouse Igf2r gene , 1999, Nature.

[83]  DNA Demethylation In Vitro Involvement of RNA , 1998, Cell.

[84]  C. Walsh,et al.  Transcription of IAP endogenous retroviruses is constrained by cytosine methylation , 1998, Nature Genetics.

[85]  J. Strouboulis,et al.  Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription , 1998, Nature Genetics.

[86]  Colin A. Johnson,et al.  Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex , 1998, Nature.

[87]  B. Turner,et al.  Histone acetylation and X inactivation. , 1998, Developmental genetics.

[88]  Howard Cedar,et al.  A role for nuclear NF–κB in B–cell–specific demethylation of the Igκ locus , 1996, Nature Genetics.

[89]  A. Razin,et al.  Establishment of Imprinted Methylation Patterns during Development , 1996 .

[90]  R. Weinberg,et al.  Suppression of intestinal neoplasia by DNA hypomethylation , 1995, Cell.

[91]  J. Sogo,et al.  Replication of transcriptionally active chromatin , 1995, Nature.

[92]  A. Bird,et al.  Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. , 1994, Genes & development.

[93]  Z. Siegfried,et al.  Spl elements protect a CpG island from de novo methylation , 1994, Nature.

[94]  H. Cedar,et al.  B cell-specific demethylation: A novel role for the intronic κ chain enhancer sequence , 1994, Cell.

[95]  H. Cedar,et al.  Developmental changes in methylation of spermatogenesis–specific genes include reprogramming in the epididymis , 1994, Nature Genetics.

[96]  Rudolf Jaenisch,et al.  Role for DNA methylation in genomic imprinting , 1993, Nature.

[97]  J. Jost,et al.  Nuclear extracts of chicken embryos promote an active demethylation of DNA by excision repair of 5-methyldeoxycytidine. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[98]  T. Bestor,et al.  Properties and localization of DNA methyltransferase in preimplantation mouse embryos: implications for genomic imprinting. , 1992, Genes & development.

[99]  H. Leonhardt,et al.  A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei , 1992, Cell.

[100]  Rudolf Jaenisch,et al.  Targeted mutation of the DNA methyltransferase gene results in embryonic lethality , 1992, Cell.

[101]  A. Razin,et al.  Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. , 1992, Genes & development.

[102]  H. Schöler,et al.  Octamania: the POU factors in murine development. , 1991, Trends in genetics : TIG.

[103]  P. Leder,et al.  Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis , 1991, Cell.

[104]  A. Razin,et al.  Demethylation of CpG islands in embryonic cells , 1991, Nature.

[105]  Z. Paroush,et al.  Dynamics of demethylation and activation of the α-actin gene in myoblasts , 1990, Cell.

[106]  A. Bird,et al.  High levels of De Novo methylation and altered chromatin structure at CpG islands in cell lines , 1990, Cell.

[107]  S. Tapscott,et al.  De novo methylation of the MyoD1 CpG island during the establishment of immortal cell lines. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[108]  W. Schaffner,et al.  Sp1 transcription factor binds DNA and activates transcription even when the binding site is CpG methylated. , 1988, Genes & development.

[109]  V. Chapman,et al.  Differences in DNA methylation during oogenesis and spermatogenesis and their persistence during early embryogenesis in the mouse. , 1987, Genes & development.

[110]  B. Luckow,et al.  CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements , 1987, Nucleic Acids Res..

[111]  A. Graessmann,et al.  Chromatin structure is required to block transcription of the methylated herpes simplex virus thymidine kinase gene. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[112]  S. Lehnert,et al.  Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. , 1987, Development.

[113]  G. Martin,et al.  Methylation of the Hprt gene on the inactive X occurs after chromosome inactivation , 1987, Cell.

[114]  R. Grainger,et al.  Delta-crystallin genes become hypomethylated in postmitotic lens cells during chicken development. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[115]  H. Cedar,et al.  Muscle-specific activation of a methylated chimeric actin gene , 1986, Cell.

[116]  S. Baylin,et al.  DNA methylation patterns of the calcitonin gene in human lung cancers and lymphomas. , 1986, Cancer research.

[117]  M. Szyf,et al.  Replacement of 5-methylcytosine by cytosine: a possible mechanism for transient DNA demethylation during differentiation. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[118]  Howard Cedar,et al.  DNA methylation affects the formation of active chromatin , 1986, Cell.

[119]  Donald Macleod,et al.  A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA , 1985, Cell.

[120]  M. Szyf,et al.  Gene Methylation Patterns and Expression , 1984 .

[121]  A. Razin,et al.  Pattern of methylation of two genes coding for housekeeping functions. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[122]  A. Feinberg,et al.  Hypomethylation distinguishes genes of some human cancers from their normal counterparts , 1983, Nature.

[123]  Michael C. Wilson,et al.  Delayed de novo methylation in teratocarcinoma suggests additional tissue-specific mechanisms for controlling gene expression , 1983, Nature.

[124]  A. Razin,et al.  In vitro methylation of the hamster adenine phosphoribosyltransferase gene inhibits its expression in mouse L cells. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[125]  A. Razin,et al.  Substrate and sequence specificity of a eukaryotic DNA methylase , 1982, Nature.

[126]  A. Razin,et al.  Clonal inheritance of the pattern of DNA methylation in mouse cells. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[127]  A. Razin,et al.  Sequence specificity of methylation in higher plant DNA , 1981, Nature.

[128]  H. Cedar,et al.  Active gene sequences are undermethylated. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[129]  Michael Wigler,et al.  The somatic replication of DNA methylation , 1981, Cell.

[130]  H. Cedar,et al.  In vitro methylation of DNA with Hpa II methylase. , 1981, Nucleic acids research.

[131]  A. Riggs,et al.  DNA methylation and gene function. , 1980, Science.

[132]  A. Razin,et al.  Methylation of foreign DNA sequences in eukaryotic cells. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[133]  R. Flavell,et al.  DNA methylation in the human γδβ-globin locus in erythroid and nonerythroid tissues , 1980, Cell.

[134]  A. Razin,et al.  Direct detection of methylated cytosine in DNA by use of the restriction enzyme MspI. , 1979, Nucleic acids research.

[135]  H. Cedar,et al.  Organization of 5-methylcytosine in chromosomal DNA. , 1978, Biochemistry.

[136]  A. Bird,et al.  Use of restriction enzymes to study eukaryotic DNA methylation: II. The symmetry of methylated sites supports semi-conservative copying of the methylation pattern. , 1978, Journal of molecular biology.

[137]  A. Razin,et al.  Distribution of 5-methylcytosine in chromatin. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[138]  R. Sinsheimer.  The action of pancreatic deoxyribonuclease. II. Isomeric dinucleotides. , 1955, The Journal of biological chemistry.