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

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Abstract

Methylation of cytosines (5^meC) 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 show an increase of relative 5^meC levels at the TSS 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.

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Marco Morselli

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

For correspondence
mmorselli@ucla.edu

Competing interests
The authors declare that no competing interests exist.
William A Pastor

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Barbara Montanini

Biochemistry and Molecular Biology Unit, Department of Life Sciences, Laboratory of Functional Genomics and Protein Engineering, Parma, Italy

Competing interests
The authors declare that no competing interests exist.
Kevin Nee

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Roberto Ferrari

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Kai Fu

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Giancarlo Bonora

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Liudmilla Rubbi

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Amander T Clark

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Simone Ottonello

Biochemistry and Molecular Biology Unit, Department of Life Sciences, Laboratory of Functional Genomics and Protein Engineering, Parma, Italy

Competing interests
The authors declare that no competing interests exist.
Steven E Jacobsen

Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Matteo Pellegrini

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal experimentation was conducted with the highest ethical standards in accordance with UCLA policy and procedures (DHHS OLAW A3196-01, AAALAC #000408 and protocol # 2008-070), and applicable provisions of the USDA Animal Welfare Act Regulations, the Public Health Service Policy on Humane Care and Use of Laboratory Animals, and the Guide for the Care and Use of Laboratory Animals.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.