In Vivo Control of CpG and Non-CpG DNA Methylation by DNA Methyltransferases

View/ Open
Author
Arand, Julia
Spieler, David
Karius, Tommy
Branco, Miguel R.
Meilinger, Daniela
Jenuwein, Thomas
Xu, Guoliang
Leonhardt, Heinrich
Wolf, Verena
Walter, Jörn
Published Version
https://doi.org/10.1371/journal.pgen.1002750Metadata
Show full item recordCitation
Arand, 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).Abstract
The 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386304/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11691835
Collections
- FAS Scholarly Articles [17553]
Contact administrator regarding this item (to report mistakes or request changes)