RT Journal Article SR Electronic T1 Phylogenetic profiling resolves early emergence of PRC2 and illuminates its functional core JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202101271 DO 10.26508/lsa.202101271 VO 5 IS 7 A1 Abdoallah Sharaf A1 Mallika Vijayanathan A1 Miroslav Oborník A1 Iva Mozgová YR 2022 UL https://www.life-science-alliance.org/content/5/7/e202101271.abstract AB Polycomb repressive complex 2 (PRC2) is involved in maintaining transcriptionally silent chromatin states through methylating lysine 27 of histone H3 by the catalytic subunit enhancer of zeste [E(z)]. 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. For the first time, we identify the putative ortholog of E(z) in Discoba, a lineage hypothetically proximal to the eukaryotic root, strongly supporting emergence of PRC2 before the diversification of eukaryotes. Analyzing 283 species, we robustly detect a common presence of E(z) and ESC, indicating a conserved functional core. Full-length Su(z)12 orthologs were identified in some lineages and species only, indicating, nonexclusively, high divergence of VEFS-Box–containing Su(z)12-like proteins, functional convergence of sequence-unrelated proteins, or Su(z)12 dispensability. Our results trace E(z) evolution within the SET-domain protein family, proposing a substrate specificity shift during E(z) evolution based on SET-domain and H3 histone interaction prediction.