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dc.contributor.authorArand, Julia
dc.contributor.authorSpieler, David
dc.contributor.authorKarius, Tommy
dc.contributor.authorBranco, Miguel R.
dc.contributor.authorMeilinger, Daniela
dc.contributor.authorMeissner, Alexander
dc.contributor.authorJenuwein, Thomas
dc.contributor.authorXu, Guoliang
dc.contributor.authorLeonhardt, Heinrich
dc.contributor.authorWolf, Verena
dc.contributor.authorWalter, Jörn
dc.date.accessioned2014-02-12T14:44:42Z
dc.date.issued2012
dc.identifier.citationArand, Julia, David Spieler, Tommy Karius, Miguel R. Branco, Daniela Meilinger, Alexander Meissner, Thomas Jenuwein, Guoliang Xu, Heinrich Leonhardt, Verena Wolf, and Jörn Walter. 2012. In vivo control of cpg and non-cpg dna methylation by dna methyltransferases. PLoS Genetics 8(6).en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11691835
dc.description.abstractThe enzymatic control of the setting and maintenance of symmetric and non-symmetric DNA methylation patterns in a particular genome context is not well understood. Here, we describe a comprehensive analysis of DNA methylation patterns generated by high resolution sequencing of hairpin-bisulfite amplicons of selected single copy genes and repetitive elements (LINE1, B1, IAP-LTR-retrotransposons, and major satellites). The analysis unambiguously identifies a substantial amount of regional incomplete methylation maintenance, i.e. hemimethylated CpG positions, with variant degrees among cell types. Moreover, non-CpG cytosine methylation is confined to ESCs and exclusively catalysed by Dnmt3a and Dnmt3b. This sequence position–, cell type–, and region-dependent non-CpG methylation is strongly linked to neighboring CpG methylation and requires the presence of Dnmt3L. The generation of a comprehensive data set of 146,000 CpG dyads was used to apply and develop parameter estimated hidden Markov models (HMM) to calculate the relative contribution of DNA methyltransferases (Dnmts) for de novo and maintenance DNA methylation. The comparative modelling included wild-type ESCs and mutant ESCs deficient for Dnmt1, Dnmt3a, Dnmt3b, or Dnmt3a/3b, respectively. The HMM analysis identifies a considerable de novo methylation activity for Dnmt1 at certain repetitive elements and single copy sequences. Dnmt3a and Dnmt3b contribute de novo function. However, both enzymes are also essential to maintain symmetrical CpG methylation at distinct repetitive and single copy sequences in ESCs.en_US
dc.description.sponsorshipStem Cell and Regenerative Biologyen_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pgen.1002750en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386304/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectGeneticsen_US
dc.subjectEpigeneticsen_US
dc.subjectDNA modificationen_US
dc.subjectGenomicsen_US
dc.subjectFunctional Genomicsen_US
dc.titleIn Vivo Control of CpG and Non-CpG DNA Methylation by DNA Methyltransferasesen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Geneticsen_US
dash.depositing.authorMeissner, Alexander
dc.date.available2014-02-12T14:44:42Z
dc.identifier.doi10.1371/journal.pgen.1002750*
dash.contributor.affiliatedMeissner, Alexander


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