A unique bipartite Polycomb signature regulates stimulus-response transcription during development

Nat Genet. 2021 Mar;53(3):379-391. doi: 10.1038/s41588-021-00789-z. Epub 2021 Feb 18.


Rapid cellular responses to environmental stimuli are fundamental for development and maturation. Immediate early genes can be transcriptionally induced within minutes in response to a variety of signals. How their induction levels are regulated and their untimely activation by spurious signals prevented during development is poorly understood. We found that in developing sensory neurons, before perinatal sensory-activity-dependent induction, immediate early genes are embedded into a unique bipartite Polycomb chromatin signature, carrying active H3K27ac on promoters but repressive Ezh2-dependent H3K27me3 on gene bodies. This bipartite signature is widely present in developing cell types, including embryonic stem cells. Polycomb marking of gene bodies inhibits mRNA elongation, dampening productive transcription, while still allowing for fast stimulus-dependent mark removal and bipartite gene induction. We reveal a developmental epigenetic mechanism regulating the rapidity and amplitude of the transcriptional response to relevant stimuli, while preventing inappropriate activation of stimulus-response genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / genetics*
  • Chromatin / metabolism
  • Embryonic Stem Cells / physiology
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Epigenesis, Genetic
  • Gene Expression Regulation, Developmental*
  • Genes, Immediate-Early*
  • Histones / metabolism
  • Mice, Transgenic
  • Mutation
  • Polycomb-Group Proteins / genetics*
  • Polycomb-Group Proteins / metabolism
  • Promoter Regions, Genetic
  • RNA Polymerase II / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rhombencephalon / drug effects
  • Rhombencephalon / embryology
  • Sensory Receptor Cells / physiology


  • Chromatin
  • Histones
  • Polycomb-Group Proteins
  • RNA, Messenger
  • histone H3 trimethyl Lys4
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse
  • RNA Polymerase II