Repression of CHROMOMETHYLASE 3 prevents epigenetic collateral damage in Arabidopsis

  1. Ranjith K Papareddy
  2. Katalin Páldi
  3. Anna D Smolka
  4. Patrick Hüther
  5. Claude Becker
  6. Michael D Nodine  Is a corresponding author
  1. Gregor Mendel Institute, Austria
  2. Gregor Mendel Institute; LMU Biocenter, Austria
  3. Gregor Mendel Institute; LMU Biocenter, Germany
  4. Gregor Mendel Institute; Wageningen University, Austria

Abstract

DNA methylation has evolved to silence mutagenic transposable elements (TEs) while typically avoiding the targeting of endogenous genes. Mechanisms that prevent DNA methyltransferases from ectopically methylating genes are expected to be of prime importance during periods of dynamic cell cycle activities including plant embryogenesis. However, virtually nothing is known regarding how DNA methyltransferase activities are precisely regulated during embryogenesis to prevent the induction of potentially deleterious and mitotically stable genic epimutations. Here, we report that microRNA-mediated repression of CHROMOMETHYLASE 3 (CMT3) and the chromatin features that CMT3 prefers help prevent ectopic methylation of thousands of genes during embryogenesis that can persist for weeks afterwards. Our results are also consistent with CMT3-induced ectopic methylation of promoters or bodies of genes undergoing transcriptional activation reducing their expression. Therefore, the repression of CMT3 prevents epigenetic collateral damage on endogenous genes. We also provide a model that may help reconcile conflicting viewpoints regarding the functions of gene-body methylation that occurs in nearly all flowering plants.

Data availability

All sequencing data generated in this study are publicly available at the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO, https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE171198.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Ranjith K Papareddy

    Gregor Mendel Institute, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  2. Katalin Páldi

    Gregor Mendel Institute, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  3. Anna D Smolka

    Gregor Mendel Institute, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  4. Patrick Hüther

    Austrian Academy of Sciences, Vienna Biocenter, Gregor Mendel Institute; LMU Biocenter, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Claude Becker

    Genetics, Gregor Mendel Institute; LMU Biocenter, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3406-4670
  6. Michael D Nodine

    Gregor Mendel Institute; Wageningen University, Vienna, Austria
    For correspondence
    michael.nodine@wur.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6204-8857

Funding

H2020 European Research Council (637888)

  • Michael D Nodine

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Richard Amasino, University of Wisconsin Madison, United States

Version history

  1. Received: April 13, 2021
  2. Accepted: July 21, 2021
  3. Accepted Manuscript published: July 23, 2021 (version 1)
  4. Accepted Manuscript updated: July 26, 2021 (version 2)
  5. Version of Record published: August 9, 2021 (version 3)

Copyright

© 2021, Papareddy 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

  • 2,038
    views
  • 323
    downloads
  • 14
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Ranjith K Papareddy
  2. Katalin Páldi
  3. Anna D Smolka
  4. Patrick Hüther
  5. Claude Becker
  6. Michael D Nodine
(2021)
Repression of CHROMOMETHYLASE 3 prevents epigenetic collateral damage in Arabidopsis
eLife 10:e69396.
https://doi.org/10.7554/eLife.69396

Share this article

https://doi.org/10.7554/eLife.69396

Further reading

    1. Genetics and Genomics
    Doo Eun Choi, Jun Wan Shin ... Jong-Min Lee
    Research Article

    An expanded CAG repeat in the huntingtin gene (HTT) causes Huntington’s disease (HD). Since the length of uninterrupted CAG repeat, not polyglutamine, determines the age-at-onset in HD, base editing strategies to convert CAG to CAA are anticipated to delay onset by shortening the uninterrupted CAG repeat. Here, we developed base editing strategies to convert CAG in the repeat to CAA and determined their molecular outcomes and effects on relevant disease phenotypes. Base editing strategies employing combinations of cytosine base editors and guide RNAs (gRNAs) efficiently converted CAG to CAA at various sites in the CAG repeat without generating significant indels, off-target edits, or transcriptome alterations, demonstrating their feasibility and specificity. Candidate BE strategies converted CAG to CAA on both expanded and non-expanded CAG repeats without altering HTT mRNA and protein levels. In addition, somatic CAG repeat expansion, which is the major disease driver in HD, was significantly decreased in the liver by a candidate BE strategy treatment in HD knock-in mice carrying canonical CAG repeats. Notably, CAG repeat expansion was abolished entirely in HD knock-in mice carrying CAA-interrupted repeats, supporting the therapeutic potential of CAG-to-CAA conversion strategies in HD and potentially other repeat expansion disorders.

    1. Cell Biology
    2. Genetics and Genomics
    Yangzi Zhao, Lijun Ren ... Zhukuan Cheng
    Research Article

    Cohesin is a multi-subunit protein that plays a pivotal role in holding sister chromatids together during cell division. Sister chromatid cohesion 3 (SCC3), constituents of cohesin complex, is highly conserved from yeast to mammals. Since the deletion of individual cohesin subunit always causes lethality, it is difficult to dissect its biological function in both mitosis and meiosis. Here, we obtained scc3 weak mutants using CRISPR-Cas9 system to explore its function during rice mitosis and meiosis. The scc3 weak mutants displayed obvious vegetative defects and complete sterility, underscoring the essential roles of SCC3 in both mitosis and meiosis. SCC3 is localized on chromatin from interphase to prometaphase in mitosis. However, in meiosis, SCC3 acts as an axial element during early prophase I and subsequently situates onto centromeric regions following the disassembly of the synaptonemal complex. The loading of SCC3 onto meiotic chromosomes depends on REC8. scc3 shows severe defects in homologous pairing and synapsis. Consequently, SCC3 functions as an axial element that is essential for maintaining homologous chromosome pairing and synapsis during meiosis.