Polycomb protein binding and looping in the ON transcriptional state

Sci Adv. 2024 Apr 26;10(17):eadn1837. doi: 10.1126/sciadv.adn1837. Epub 2024 Apr 24.

Abstract

Polycomb group (PcG) proteins mediate epigenetic silencing of important developmental genes by modifying histones and compacting chromatin through two major protein complexes, PRC1 and PRC2. These complexes are recruited to DNA by CpG islands (CGIs) in mammals and Polycomb response elements (PREs) in Drosophila. When PcG target genes are turned OFF, PcG proteins bind to PREs or CGIs, and PREs serve as anchors that loop together and stabilize gene silencing. Here, we address which PcG proteins bind to PREs and whether PREs mediate looping when their targets are in the ON transcriptional state. While the binding of most PcG proteins decreases at PREs in the ON state, one PRC1 component, Ph, remains bound. Further, PREs can loop to each other and with presumptive enhancers in the ON state and, like CGIs, may act as tethering elements between promoters and enhancers. Overall, our data suggest that PREs are important looping elements for developmental loci in both the ON and OFF states.

Publication types

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

MeSH terms

  • Animals
  • Chromatin / genetics
  • Chromatin / metabolism
  • CpG Islands
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Polycomb-Group Proteins* / genetics
  • Polycomb-Group Proteins* / metabolism
  • Promoter Regions, Genetic
  • Protein Binding*
  • Response Elements*
  • Transcription, Genetic*

Substances

  • Polycomb-Group Proteins
  • Drosophila Proteins
  • Chromatin