CpNpG methylation in mammalian cells

In vertebrate DMA, 3% to 5% of cytosine residues are present as 5–methylcytosine, and it is generally accepted that essentially all of this methylation occurs at cytosines which are contained in the symmetrical dinucleotide CpG. In this report we demonstrate, using bisulphite genomic sequencing, that the methylation machinery of mammalian cells is capable of both maintenance and de novo methylation at CpNpG sites. The existence of inherited CpNpG methylation in mammalian cells has important implications in gene regulation and in the aetiology of disease

[1]  P. Meyer,et al.  Evidence for cytosine methylation of non‐symmetrical sequences in transgenic Petunia hybrida. , 1994, The EMBO journal.

[2]  T. Trautner,et al.  High plasticity of multispecific DNA methyltransferases in the region carrying DNA target recognizing enzyme modules. , 1992, The EMBO journal.

[3]  W. Doerfler,et al.  Establishment of de novo DNA methylation patterns. Transcription factor binding and deoxycytidine methylation at CpG and non-CpG sequences in an integrated adenovirus promoter. , 1990, Journal of molecular biology.

[4]  A. Riggs,et al.  Methylation analysis by genomic sequencing of 5′ region of mousePgk-1 gene and a cautionary note concerning the method , 1993, Somatic cell and molecular genetics.

[5]  A. Graessmann,et al.  Are there two DNA methyltransferase gene families in plant cells? A new potential methyltransferase gene isolated from an Arabidopsis thaliana genomic library. , 1994, Nucleic Acids Research.

[6]  B. Wold,et al.  Genomic sequencing and methylation analysis by ligation mediated PCR. , 1989, Science.

[7]  H. Lehrach,et al.  Trinucleotide repeat expansions and human genetic disease. , 1994, BioEssays : news and reviews in molecular, cellular and developmental biology.

[8]  V. Ingram,et al.  Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[9]  M. Surani,et al.  DNA methylation and genomic imprinting in mammals. , 1993, EXS.

[10]  B. Trask,et al.  Isolation and characterization of the cDNA encoding human DNA methyltransferase. , 1992, Nucleic acids research.

[11]  R. Jaenisch,et al.  Retrovirus genomes methylated by mammalian but not bacterial methylase are non-infectious , 1983, Nature.

[12]  A. Levine,et al.  Alterations in the developmental potential of embryonal carcinoma cells in mixed aggregates of nullipotent and pluripotent cells , 1979, Cell.

[13]  H. Leonhardt,et al.  Structure, function and regulation of mammalian DNA methyltransferase. , 1993, EXS.

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

[15]  T. Bestor,et al.  Activation of mammalian DNA methyltransferase by cleavage of a Zn binding regulatory domain. , 1992, The EMBO journal.

[16]  T. Trautner,et al.  Methylation of DNA in prokaryotes. , 1993, EXS.

[17]  A. Bird,et al.  Use of restriction enzymes to study eukaryotic DNA methylation: I. The methylation pattern in ribosomal DNA from Xenopus laevis. , 1978, Journal of molecular biology.

[18]  L. E. McDonald,et al.  A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

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

[20]  J. P. Jost,et al.  DNA Methylation: Molecular Biology and Biological Significance , 1993 .

[21]  S. Clark,et al.  High sensitivity mapping of methylated cytosines. , 1994, Nucleic acids research.

[22]  V. Ingram,et al.  Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. , 1988, Journal of molecular biology.

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

[24]  E. Tasheva,et al.  Densely methylated DNA islands in mammalian chromosomal replication origins , 1994, Molecular and cellular biology.

[25]  E. Dennis,et al.  Isolation and identification by sequence homology of a putative cytosine methyltransferase from Arabidopsis thaliana. , 1993, Nucleic acids research.

[26]  S. Clark,et al.  Direct cloning of polymerase chain reaction products in an XcmI T-vector. , 1994, Analytical biochemistry.

[27]  E. Selker Control of DNA methylation in fungi. , 1993, EXS.

[28]  T. Bestor,et al.  DNA methylation: evolution of a bacterial immune function into a regulator of gene expression and genome structure in higher eukaryotes. , 1990, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[29]  G. Church,et al.  Genomic sequencing. , 1993, Methods in molecular biology.

[30]  J. Jost,et al.  A simple high-resolution procedure to study DNA methylation and in vivo DNA-protein interactions on a single-copy gene level in higher eukaryotes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[31]  M. Monk,et al.  Decrease in DNA methylase activity during preimplantation development in the mouse. , 1991, Development.

[32]  A. Graessmann,et al.  DNA methylation, chromatin structure and the regulation of gene expression. , 1993, EXS.

[33]  J. Jost,et al.  Genomic footprinting with Taq polymerase , 1989, Nature.

[34]  W. Diver,et al.  The majority of methylated deoxycytidines in human DNA are not in the CpG dinucleotide. , 1987, Biochemical and biophysical research communications.