1. Developmental Biology
  2. Genetics and Genomics
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In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse

  1. Marco Morselli  Is a corresponding author
  2. William A Pastor
  3. Barbara Montanini
  4. Kevin Nee
  5. Roberto Ferrari
  6. Kai Fu
  7. Giancarlo Bonora
  8. Liudmilla Rubbi
  9. Amander T Clark
  10. Simone Ottonello
  11. Steven E Jacobsen
  12. Matteo Pellegrini
  1. University of California, Los Angeles, United States
  2. Laboratory of Functional Genomics and Protein Engineering, Italy
Research Article
  • Cited 85
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Cite this article as: eLife 2015;4:e06205 doi: 10.7554/eLife.06205

Abstract

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 show an increase of relative 5meC 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.

Article and author information

Author details

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.

Reviewing Editor

  1. Bing Ren, University of California, San Diego School of Medicine, United States

Publication history

  1. Received: December 20, 2014
  2. Accepted: April 2, 2015
  3. Accepted Manuscript published: April 7, 2015 (version 1)
  4. Accepted Manuscript updated: April 8, 2015 (version 2)
  5. Version of Record published: April 29, 2015 (version 3)
  6. Version of Record updated: August 31, 2017 (version 4)

Copyright

© 2015, Morselli et al.

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.

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Further reading

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    2. Stem Cells and Regenerative Medicine
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    During whole-body regeneration, a bisection injury can trigger two different types of regeneration. To understand the transcriptional regulation underlying this adaptive response, we characterized transcript abundance and chromatin accessibility during oral and aboral regeneration in the cnidarian Hydra vulgaris. We found that the initial response to amputation at both wound sites is identical and includes widespread apoptosis and the activation of the oral-specifying Wnt signaling pathway. By 8 hr post amputation, Wnt signaling became restricted to oral regeneration. Wnt pathway genes were also upregulated in puncture wounds, and these wounds induced the formation of ectopic oral structures if pre-existing organizers were simultaneously amputated. Our work suggests that oral patterning is activated as part of a generic injury response in Hydra, and that alternative injury outcomes are dependent on signals from the surrounding tissue. Furthermore, Wnt signaling is likely part of a conserved wound response predating the split of cnidarians and bilaterians.