A Polycomb repressive complex is required for RNAi-mediated heterochromatin formation and dynamic distribution of nuclear bodies

Nucleic Acids Res. 2021 Jun 4;49(10):5407-5425. doi: 10.1093/nar/gkaa1262.

Abstract

Polycomb group (PcG) proteins are widely utilized for transcriptional repression in eukaryotes. Here, we characterize, in the protist Tetrahymena thermophila, the EZL1 (E(z)-like 1) complex, with components conserved in metazoan Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2). The EZL1 complex is required for histone H3 K27 and K9 methylation, heterochromatin formation, transposable element control, and programmed genome rearrangement. The EZL1 complex interacts with EMA1, a helicase required for RNA interference (RNAi). This interaction is implicated in co-transcriptional recruitment of the EZL1 complex. Binding of H3K27 and H3K9 methylation by PDD1-another PcG protein interacting with the EZL1 complex-reinforces its chromatin association. The EZL1 complex is an integral part of Polycomb bodies, which exhibit dynamic distribution in Tetrahymena development: Their dispersion is driven by chromatin association, while their coalescence by PDD1, likely via phase separation. Our results provide a molecular mechanism connecting RNAi and Polycomb repression, which coordinately regulate nuclear bodies and reorganize the genome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromatin Assembly and Disassembly
  • Heterochromatin / metabolism*
  • Histones / metabolism
  • Polycomb Repressive Complex 1 / metabolism*
  • Polycomb Repressive Complex 2 / metabolism*
  • Protein Processing, Post-Translational
  • Protozoan Proteins / metabolism*
  • RNA Interference*
  • Tetrahymena thermophila / genetics*

Substances

  • Heterochromatin
  • Histones
  • Pdd1 protein, Tetrahymena
  • Protozoan Proteins
  • Polycomb Repressive Complex 2
  • Polycomb Repressive Complex 1