Phylogenetic profiling resolves early emergence of PRC2 and illuminates its functional core

Life Sci Alliance. 2022 Apr 19;5(7):e202101271. doi: 10.26508/lsa.202101271. Print 2022 Jul.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drosophila Proteins* / metabolism
  • Histones / genetics
  • Histones / metabolism
  • Lysine / metabolism
  • Phylogeny
  • Polycomb Repressive Complex 2* / genetics
  • Polycomb Repressive Complex 2* / metabolism


  • Drosophila Proteins
  • Histones
  • Polycomb Repressive Complex 2
  • Lysine

Associated data

  • PDB/7KSR