Methylation-sensitive expression of a DNA demethylase gene serves as an epigenetic rheostat

PLoS Genet. 2015 Mar 31;11(3):e1005142. doi: 10.1371/journal.pgen.1005142. eCollection 2015 Mar.

Abstract

Genomes must balance active suppression of transposable elements (TEs) with the need to maintain gene expression. In Arabidopsis, euchromatic TEs are targeted by RNA-directed DNA methylation (RdDM). Conversely, active DNA demethylation prevents accumulation of methylation at genes proximal to these TEs. It is unknown how a cellular balance between methylation and demethylation activities is achieved. Here we show that both RdDM and DNA demethylation are highly active at a TE proximal to the major DNA demethylase gene ROS1. Unexpectedly, and in contrast to most other genomic targets, expression of ROS1 is promoted by DNA methylation and antagonized by DNA demethylation. We demonstrate that inducing methylation in the ROS1 proximal region is sufficient to restore ROS1 expression in an RdDM mutant. Additionally, methylation-sensitive expression of ROS1 is conserved in other species, suggesting it is adaptive. We propose that the ROS1 locus functions as an epigenetic rheostat, tuning the level of demethylase activity in response to methylation alterations, thus ensuring epigenomic stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis
  • Arabidopsis Proteins / biosynthesis
  • Arabidopsis Proteins / genetics*
  • DNA Methylation / genetics*
  • DNA Transposable Elements / genetics
  • Epigenomics*
  • Gene Expression Regulation, Plant
  • Gene Silencing
  • Genome, Plant
  • Genomic Instability / genetics
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Plants, Genetically Modified
  • Seedlings / genetics
  • Seedlings / growth & development
  • Transcription, Genetic*

Substances

  • Arabidopsis Proteins
  • DNA Transposable Elements
  • Nuclear Proteins
  • ROS1 protein, Arabidopsis

Grant support

This work was funded by the Pew Charitable Trust's Pew Biomedical Scholars award and the Alexander and Margaret Stewart Trust's Scholars award to MG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.