In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse

Methylation of cytosines (5(me)C) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves of de novo DNA methylation. In vivo mechanisms of DNA methylation establishment are largely uncharacterized. Here, we use Saccharomyces ce...

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Bibliographic Details
Published in:eLife 2015-04, Vol.4, p.e06205-e06205
Main Authors: Morselli, Marco, Pastor, William A, Montanini, Barbara, Nee, Kevin, Ferrari, Roberto, Fu, Kai, Bonora, Giancarlo, Rubbi, Liudmilla, Clark, Amander T, Ottonello, Simone, Jacobsen, Steven E, Pellegrini, Matteo
Format: Article
Language:English
Subjects:
Animals
Cell division
Chromatin
Chromatin - chemistry
Chromatin - metabolism
CpG Islands
Cytosine - metabolism
Demethylation
Deoxyribonucleic acid
Developmental Biology and Stem Cells
DNA
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA Methylation
DNA Methyltransferase 3B
DNMT3
Embryo, Mammalian
Gene expression
Gene Expression Regulation, Developmental
Genetic Vectors
Genomes
Genomics
Genomics and Evolutionary Biology
Germ Cells
H3K36me3
H3K4me3
histone
Histone-Lysine N-Methyltransferase - deficiency
Histone-Lysine N-Methyltransferase - genetics
Histones - genetics
Histones - metabolism
Male
Mammals
Methyltransferases - deficiency
Methyltransferases - genetics
Mice
Open Reading Frames
Protein Isoforms - genetics
Protein Isoforms - metabolism
Proteins
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Signal Transduction
Stem cells
Transcription
Transcription Initiation Site
Transformation, Genetic
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Summary:Methylation of cytosines (5(me)C) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves of de novo DNA methylation. In vivo mechanisms of DNA methylation establishment are largely uncharacterized. Here, we use Saccharomyces cerevisiae as a system lacking DNA methylation to define the chromatin features influencing the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4 methylation are mutually exclusive and that DNMT3B is co-localized with H3K36 methylated regions. In support of this observation, DNA methylation analysis in yeast strains without Set1 and Set2 shows an increase of relative 5(me)C levels at the transcription start site and a decrease in the gene-body, respectively. We extend our observation to the murine male germline, where H3K4me3 is strongly anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These results show the importance of H3K36 methylation for gene-body DNA methylation in vivo.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.06205