DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes

Elife. 2017 Nov 15;6:e30674. doi: 10.7554/eLife.30674.

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.

Keywords: A. thaliana; DDM1; DNA methylation; chromosomes; genes; mouse; nucleosome; plant biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arabidopsis / metabolism*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • DNA / metabolism*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Methylation*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Mice
  • Nucleosomes / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Arabidopsis Proteins
  • DDM1 protein, Arabidopsis
  • DNA-Binding Proteins
  • Nucleosomes
  • Transcription Factors
  • DNA
  • DNA Helicases
  • lymphoid specific helicase, mouse