Novel crosstalk between DNA methylation and H3K27me3 revealed at Arabidopsis transposable elements

Transposable elements (TEs) are primarily silenced by DNA methylation and the associated histone modification H3K9me2 in many multicellular eukaryotes, including plants. However, in the absence of DNA methylation due to mutations in the DNA methylation machinery or in certain developmental contexts, the same TEs can gain Polycomb-associated H3K27me3, another epigenetic silencing mark that is usually linked with the facultative silencing of genes. In this study, we initially aimed to investigate whether DNA methylation and H3K27me3 could compete during the establishment of silencing at TEs in the model plant Arabidopsis. Strikingly, we show that the deposition of the H3K27me3 mark at newly inserted transgenic TE sequences is impaired in plants in which the de novo DNA methyltransferase DRM2 is mutated, contrary to the competition model hypothesized. Further profiling of H3K27me3 in drm2 mutants and in the DNA demethylase mutant rdd confirmed this new role of DNA methylation in promoting H3K27me3 deposition at some loci, in addition to the previously described antagonistic role at others; these findings further reveal a new function of DNA demethylation in modulating H3K27me3 levels in vegetative tissues. Finally, by implementing targeted DNA methylation experiments, we demonstrate that DNA methylation has a direct impact on PcG recruitment and can either promote H3K27me3 deposition or antagonize it in a locus-specific manner. Together, our results uncover a novel crosstalk between DNA methylation and Polycomb and reveal that these two pathways, thought to be specialized and antagonistic, can be interdependent and cooperate more than anticipated to maintain genome and epigenome integrity in eukaryotes.