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

Arand, J., Spieler, D., Karius, T., Branco, M. R., Meilinger, D., Meissner, A., et al. (2012). In vivo Control of CpG and Non-CpG DNA Methylation by DNA Methyltransferases. PLoS Genetics, 8: e1002750. doi:10.1371/journal.pgen.1002750.

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 Creators:
Arand, Julia1, Author
Spieler, David1, Author
Karius, Tommy1, Author
Branco, Miguel R.1, Author
Meilinger, Daniela1, Author
Meissner, Alexander1, Author
Jenuwein, Thomas2, Author              
Xu, Guoliang1, Author
Leonhardt, Heinrich1, Author
Wolf, Verena1, Author
Walter, Jörn1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              

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 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.

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Language(s): eng - English
 Dates: 2012-06-282012
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1371/journal.pgen.1002750
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Title: PLoS Genetics
  Other : PLoS Genet.
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 8 Sequence Number: e1002750 Start / End Page: - Identifier: ISSN: 1553-7390
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000017180