Common alleles of CMT2 and NRPE1 are major determinants of CHH methylation variation in Arabidopsis thaliana

PLoS Genet. 2019 Dec 30;15(12):e1008492. doi: 10.1371/journal.pgen.1008492. eCollection 2019 Dec.


DNA cytosine methylation is an epigenetic mark associated with silencing of transposable elements (TEs) and heterochromatin formation. In plants, it occurs in three sequence contexts: CG, CHG, and CHH (where H is A, T, or C). The latter does not allow direct inheritance of methylation during DNA replication due to lack of symmetry, and methylation must therefore be re-established every cell generation. Genome-wide association studies (GWAS) have previously shown that CMT2 and NRPE1 are major determinants of genome-wide patterns of TE CHH methylation. Here we instead focus on CHH methylation of individual TEs and TE-families, allowing us to identify the pathways involved in CHH methylation simply from natural variation and confirm the associations by comparing them with mutant phenotypes. Methylation at TEs targeted by the RNA-directed DNA methylation (RdDM) pathway is unaffected by CMT2 variation, but is strongly affected by variation at NRPE1, which is largely responsible for the longitudinal cline in this phenotype. In contrast, CMT2-targeted TEs are affected by both loci, which jointly explain 7.3% of the phenotypic variation (13.2% of total genetic effects). There is no longitudinal pattern for this phenotype, however, because the geographic patterns appear to compensate for each other in a pattern suggestive of stabilizing selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / genetics*
  • Arabidopsis Proteins / genetics
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methylation*
  • DNA Transposable Elements*
  • DNA-Directed RNA Polymerases / genetics*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Plant
  • Genetic Loci
  • Genetic Variation
  • Genome-Wide Association Study
  • Phenotype
  • Sequence Analysis, DNA


  • Arabidopsis Proteins
  • DNA Transposable Elements
  • DNA (Cytosine-5-)-Methyltransferases
  • chromomethylase
  • DNA-Directed RNA Polymerases

Grant support

This work was funded in part by ERC AdvG 789037 EPICLINES to MN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.