Genome-wide negative feedback drives transgenerational DNA methylation dynamics in Arabidopsis

PLoS Genet. 2015 Apr 22;11(4):e1005154. doi: 10.1371/journal.pgen.1005154. eCollection 2015 Apr.

Abstract

Epigenetic variations of phenotypes, especially those associated with DNA methylation, are often inherited over multiple generations in plants. The active and inactive chromatin states are heritable and can be maintained or even be amplified by positive feedback in a transgenerational manner. However, mechanisms controlling the transgenerational DNA methylation dynamics are largely unknown. As an approach to understand the transgenerational dynamics, we examined long-term effect of impaired DNA methylation in Arabidopsis mutants of the chromatin remodeler gene DDM1 (Decrease in DNA Methylation 1) through whole genome DNA methylation sequencing. The ddm1 mutation induces a drastic decrease in DNA methylation of transposable elements (TEs) and repeats in the initial generation, while also inducing ectopic DNA methylation at hundreds of loci. Unexpectedly, this ectopic methylation can only be seen after repeated self-pollination. The ectopic cytosine methylation is found primarily in the non-CG context and starts from 3' regions within transcription units and spreads upstream. Remarkably, when chromosomes with reduced DNA methylation were introduced from a ddm1 mutant into a DDM1 wild-type background, the ddm1-derived chromosomes also induced analogous de novo accumulation of DNA methylation in trans. These results lead us to propose a model to explain the transgenerational DNA methylation redistribution by genome-wide negative feedback. The global negative feedback, together with local positive feedback, would ensure robust and balanced differentiation of chromatin states within the genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis
  • Arabidopsis Proteins / biosynthesis
  • Arabidopsis Proteins / genetics*
  • Chromatin / genetics
  • Chromatin Assembly and Disassembly / genetics
  • Cytosine
  • DNA Methylation / genetics*
  • DNA Transposable Elements / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Epigenesis, Genetic
  • Feedback, Physiological*
  • Gene Expression Regulation, Plant
  • Genome, Plant*
  • Mutation
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*

Substances

  • Arabidopsis Proteins
  • Chromatin
  • DDM1 protein, Arabidopsis
  • DNA Transposable Elements
  • DNA-Binding Proteins
  • Transcription Factors
  • Cytosine

Associated data

  • GEO/GSE37106
  • GEO/GSE37284

Grants and funding

This work was supported by grants from the Mitsubishi Foundation (to TK), the Japanese Ministry of Education, Culture, Sports, Science and Technology (19207002 and 19060014, to TK) Systems Functional Genetics Project of the Transdisciplinary Research Integration Center, Research Organization of Information and Systems, Japan (to YT, AT, AF and TK), the European Union Seventh Framework Programme Network of Excellence EpiGeneSys (Award 257082, to VC), and the Investissements d’Avenir ANR-10-LABX-54 MEMO LIFE as well as ANR-11-IDEX-0001-02 PSL* Research University (to VC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.