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

Marco Morselli; William A Pastor; Barbara Montanini; Kevin Nee; Roberto Ferrari; Kai Fu; Giancarlo Bonora; Liudmilla Rubbi; Amander T Clark; Simone Ottonello; Steven E Jacobsen; Matteo Pellegrini

doi:10.7554/eLife.06205

eLife (Apr 2015)

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

Marco Morselli,
William A Pastor,
Barbara Montanini,
Kevin Nee,
Roberto Ferrari,
Kai Fu,
Giancarlo Bonora,
Liudmilla Rubbi,
Amander T Clark,
Simone Ottonello,
Steven E Jacobsen,
Matteo Pellegrini

Affiliations

Marco Morselli: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
William A Pastor: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Barbara Montanini: Biochemistry and Molecular Biology Unit, Department of Life Sciences, Laboratory of Functional Genomics and Protein Engineering, Parma, Italy
Kevin Nee: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Roberto Ferrari: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Kai Fu: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Giancarlo Bonora: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United States
Liudmilla Rubbi: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Amander T Clark: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Simone Ottonello: Biochemistry and Molecular Biology Unit, Department of Life Sciences, Laboratory of Functional Genomics and Protein Engineering, Parma, Italy
Steven E Jacobsen: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United States; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
Matteo Pellegrini: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United States

DOI: https://doi.org/10.7554/eLife.06205
Journal volume & issue: Vol. 4

Abstract

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Methylation of cytosines (5meC) 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 5meC 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.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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Abstract

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