Abstract
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.
Highlights
In multicellular organisms, every cell type possesses the same genetic information, but manifests a different phenotype
We demonstrate that the pattern of H3K4 and H3K36 methylation in embryonic male germ cells accurately predicts which regions undergo de novo methylation, indicating that the mechanism observed in yeast is conserved in mammals
Our study aimed to identify chromatin features that affect the activity of mammalian de novo DNMTs in the establishment of DNA methylation
Summary
Every cell type possesses the same genetic information, but manifests a different phenotype. Many players contribute to chromatin states, including nucleosome organization, histone post-translational modifications, and non-coding RNAs (Chen and Dent, 2014; Maze et al, 2014; Quinodoz and Guttman, 2014). Another mechanism for maintaining the state of a cell through cell division is the methylation of cytosines at position 5 (5meC), a widespread heritable DNA modification found in prokaryotes, plants, several fungi, and animals (Iyer et al, 2011). DNA methylation plays a fundamental role in processes such as imprinting, X-chromosome inactivation, transposon inactivation, and gene expression regulation (Smith and Meissner, 2013). Dysregulation of DNA methylation is a common feature in cancer (Eden et al, 2003; You and Jones, 2012) and a variety of human diseases are caused by defective imprinting (Peters, 2014)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
