The Polycomb protein Ezl1 mediates H3K9 and H3K27 methylation to repress transposable elements in Paramecium

Andrea Frapporti,Linda Sperling,Takayuki Kawaguchi,Evangelia Eleftheriou,Karine Guitot,Damarys Loew,Raphaël Margueron,Sandra Duharcourt,Daniel Holoch,Caridad Miró Pina,Bérangère Lombard,Olivier Arnaiz,Adeline Humbert

doi:10.1038/s41467-019-10648-5

Abstract

In animals and plants, the H3K9me3 and H3K27me3 chromatin silencing marks are deposited by different protein machineries. H3K9me3 is catalyzed by the SET-domain SU(VAR)3–9 enzymes, while H3K27me3 is catalyzed by the SET-domain Enhancer-of-zeste enzymes, which are the catalytic subunits of Polycomb Repressive Complex 2 (PRC2). Here, we show that the Enhancer-of-zeste-like protein Ezl1 from the unicellular eukaryote Paramecium tetraurelia, which exhibits significant sequence and structural similarities with human EZH2, catalyzes methylation of histone H3 in vitro and in vivo with an apparent specificity toward K9 and K27. We find that H3K9me3 and H3K27me3 co-occur at multiple families of transposable elements in an Ezl1-dependent manner. We demonstrate that loss of these histone marks results in global transcriptional hyperactivation of transposable elements with modest effects on protein-coding gene expression. Our study suggests that although often considered functionally distinct, H3K9me3 and H3K27me3 may share a common evolutionary history as well as a common ancestral role in silencing transposable elements.

Highlights

IntroductionThe H3K9me[3] and H3K27me[3] chromatin silencing marks are deposited by different protein machineries
In animals and plants, the H3K9me[3] and H3K27me[3] chromatin silencing marks are deposited by different protein machineries
To examine the chromatin states of transposable elements more globally, we focused our analysis on the distribution of H3K9me[3], H3K27me[3], and H3K4me[3] marks by chromatin immunoprecipitation followed by deep-sequencing (ChIP-seq) in biological replicates upon PGM knockdown (Supplementary Table 5)

Summary

Introduction

The H3K9me[3] and H3K27me[3] chromatin silencing marks are deposited by different protein machineries. H3K9me[3] is catalyzed by the SET-domain SU(VAR)[3,4,5,6,7,8,9] enzymes, while H3K27me[3] is catalyzed by the SET-domain Enhancer-of-zeste enzymes, which are the catalytic subunits of Polycomb Repressive Complex 2 (PRC2). Post translational modifications of histones play essential roles in DNA transactions at the level of chromatin Among these modifications, trimethylation of histone H3 on lysine 9 (H3K9me3) and lysine 27 (H3K27me3) are typically associated with transcriptionally silent chromatin. H3K9me[3] is catalyzed by the SET-domain SU(VAR) 3–9 enzymes[1,2,3,4,5], while H3K27me[3] is installed by the SET-domain Enhancer-of-zeste enzymes, acting as the catalytic subunits of Polycomb Repressive Complex 2 (PRC2)[6,7,8,9]. Whether H3K27 and H3K9 trimethylation exert overlapping roles under physiological circumstances remains an open question

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