DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes
Abstract
Cytosine methylation regulates essential genome functions across eukaryotes, but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved. Here, we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome, suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases in vivo. Furthermore, we show that simultaneous mutation of DDM1 and linker histone H1 in Arabidopsis reproduces the strong linker-specific methylation patterns of species that diverged from flowering plants and animals over a billion years ago. Our results indicate that in the absence of remodeling, nucleosomes are strong barriers to DNA methyltransferases. Linker-specific methylation can evolve simply by breaking the connection between nucleosome remodeling and DNA methylation.
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Funding
Howard Hughes Medical Institute
- Daniel Zilberman
Horizon 2020 Framework Programme
- Daniel Zilberman
National Institutes of Health
- David B Lyons
Helen Hay Whitney Foundation
- David B Lyons
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Richard Amasino, University of Wisconsin, United States
Version history
- Received: July 24, 2017
- Accepted: November 14, 2017
- Accepted Manuscript published: November 15, 2017 (version 1)
- Version of Record published: December 13, 2017 (version 2)
Copyright
© 2017, Lyons & Zilberman
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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