1. Developmental Biology
  2. Genetics and Genomics

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
https://doi.org/10.7554/eLife.06205
Share this article
Cite this article
  1. Marco Morselli
  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
(2015)
In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse
eLife 4:e06205.
https://doi.org/10.7554/eLife.06205
  2. Download BibTeX
  3. Download .RIS

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

Version 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.

Metrics

  • 7,107
    Page views
  • 1,414
    Downloads
  • 121
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Marco Morselli
  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
(2015)
In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse
eLife 4:e06205.
https://doi.org/10.7554/eLife.06205

Categories and tags

Research organisms

Further reading

    1. Computational and Systems Biology
    2. Developmental Biology

    A comprehensive model of Drosophila epithelium reveals the role of embryo geometry and cell topology in mechanical responses

    Mohamad Ibrahim Cheikh, Joel Tchoufag ... Konstantin Doubrovinski
    Research Article

    In order to understand morphogenesis, it is necessary to know the material properties or forces shaping the living tissue. In spite of this need, very few in vivo measurements are currently available. Here, using the early Drosophila embryo as a model, we describe a novel cantilever-based technique which allows for the simultaneous quantification of applied force and tissue displacement in a living embryo. By analyzing data from a series of experiments in which embryonic epithelium is subjected to developmentally relevant perturbations, we conclude that the response to applied force is adiabatic and is dominated by elastic forces and geometric constraints, or system size effects. Crucially, computational modeling of the experimental data indicated that the apical surface of the epithelium must be softer than the basal surface, a result which we confirmed experimentally. Further, we used the combination of experimental data and comprehensive computational model to estimate the elastic modulus of the apical surface and set a lower bound on the elastic modulus of the basal surface. More generally, our investigations revealed important general features that we believe should be more widely addressed when quantitatively modeling tissue mechanics in any system. Specifically, different compartments of the same cell can have very different mechanical properties; when they do, they can contribute differently to different mechanical stimuli and cannot be merely averaged together. Additionally, tissue geometry can play a substantial role in mechanical response, and cannot be neglected.

    1. Developmental Biology
    2. Evolutionary Biology

    Hierarchical morphogenesis of swallowtail butterfly wing scale nanostructures

    Kwi Shan Seah, Vinodkumar Saranathan
    Research Article

    The study of color patterns in the animal integument is a fundamental question in biology, with many lepidopteran species being exemplary models in this endeavor due to their relative simplicity and elegance. While significant advances have been made in unraveling the cellular and molecular basis of lepidopteran pigmentary coloration, the morphogenesis of wing scale nanostructures involved in structural color production is not well understood. Contemporary research on this topic largely focuses on a few nymphalid model taxa (e.g., Bicyclus, Heliconius), despite an overwhelming diversity in the hierarchical nanostructural organization of lepidopteran wing scales. Here, we present a time-resolved, comparative developmental study of hierarchical scale nanostructures in Parides eurimedes and five other papilionid species. Our results uphold the putative conserved role of F-actin bundles in acting as spacers between developing ridges, as previously documented in several nymphalid species. Interestingly, while ridges are developing in P. eurimedes, plasma membrane manifests irregular mesh-like crossribs characteristic of Papilionidae, which delineate the accretion of cuticle into rows of planar disks in between ridges. Once the ridges have grown, disintegrating F-actin bundles appear to reorganize into a network that supports the invagination of plasma membrane underlying the disks, subsequently forming an extruded honeycomb lattice. Our results uncover a previously undocumented role for F-actin in the morphogenesis of complex wing scale nanostructures, likely specific to Papilionidae.