Phylogenetic profiling suggests early origin of the core subunits of Polycomb Repressive Complex 2 (PRC2)

Abstract

Polycomb Repressive Complex 2 (PRC2) is involved in establishing transcriptionally silent chromatin states through its ability to methylate lysine 27 of histone H3 by the catalytic subunit Enhancer of zeste [E(z)]. Polycomb group (PcG) proteins play a crucial role in the maintenance of cell identity and in developmental regulation. Previously, the diversity of PRC2 subunits within some eukaryotic lineages has been reported and its presence in early eukaryotic evolution has been hypothesized. So far however, systematic survey of the presence of PRC2 subunits in species of all eukaryotic lineages is missing. Here, we report the diversity of PRC2 core subunit proteins in different eukaryotic supergroups with emphasis on the early-diverged lineages and explore the molecular evolution of PRC2 subunits by phylogenetics. In detail, we investigate the SET-domain protein sequences and their evolution across the four domains of life and particularly focus on the structural diversity of the SET-domain subfamily containing E(z), the catalytic subunit of PRC2. We show that PRC2 subunits are already present in early eukaryotic lineages, strengthening the support for PRC2 emergence prior to diversification of eukaryotes. We identify a common presence of E(z) and ESC, suggesting that Su(z)12 may have emerged later and/or may be dispensable from the evolutionarily conserved functional core of PRC2. Furthermore, our results broaden our understanding of the E(z) evolution within the SET-domain protein family, suggesting possibilities of function evolution. Through this, we shed light on a possible emerging point of the PRC2 and the evolution of its function in eukaryotes.

Caenorhabditis elegans MES-3 is a highly divergent ortholog of the canonical PRC2 component SUZ12

“…We manually inspected these orthology assignments based on consistency, which was further corroborated as the predicted occurrences of PRC2 subunits inferred from our assignments consistently matched those published previously (e.g. ( Schuettengruber et al., 2017 ; Sharaf et al., 2021 )).…”

Caenorhabditis elegansMES-3 is a highly divergent ortholog of the canonical PRC2 component SUZ12

“…We predicted the occurrence of orthologous sequences of the PRC2 core components in diverse Metazoans based on previously computed ortholog assignments from Orthofinder 31 , Broccoli 32 , EggNOG 33 , and SonicParanoid 34 on a set of reference animal genomes 35 . We manually inspected these orthology assignments based on consistency, which was further corroborated as the predicted occurrences of PRC2 subunits inferred from our assignments consistently matched those published previously (e.g., ref 36,37 ).…”

The Czech Plant Nucleus Workshop 2021

“…Among the crucial developmental and cell identity modulators in plants as well as animals are the Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2) that establish two key repressive histone post-translational modifications H2Aub and H3K27me3, respectively (Bieluszewski et al 2021). A. Sharaf and V. Mallika (BC) presented the identification of the components of PRC2 complexes in the basal eukaryotes (Sharaf et al 2021) and algae of the green lineage. M.G.…”