NF-κB dynamics determine the stimulus specificity of epigenomic reprogramming in macrophages

Science. 2021 Jun 18;372(6548):1349-1353. doi: 10.1126/science.abc0269.


The epigenome of macrophages can be reprogrammed by extracellular cues, but the extent to which different stimuli achieve this is unclear. Nuclear factor κB (NF-κB) is a transcription factor that is activated by all pathogen-associated stimuli and can reprogram the epigenome by activating latent enhancers. However, we show that NF-κB does so only in response to a subset of stimuli. This stimulus specificity depends on the temporal dynamics of NF-κB activity, in particular whether it is oscillatory or non-oscillatory. Non-oscillatory NF-κB opens chromatin by sustained disruption of nucleosomal histone-DNA interactions, enabling activation of latent enhancers that modulate expression of immune response genes. Thus, temporal dynamics can determine a transcription factor's capacity to reprogram the epigenome in a stimulus-specific manner.

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

  • Animals
  • Cell Nucleus / metabolism
  • Chromatin / metabolism
  • DNA / metabolism
  • Enhancer Elements, Genetic
  • Epigenome*
  • Gene Expression Regulation
  • Histones / metabolism
  • MAP Kinase Signaling System
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Methylation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • NF-KappaB Inhibitor alpha / genetics
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / metabolism*
  • Nucleosomes / metabolism
  • Signal Transduction
  • Transcription Factor RelA / metabolism*
  • Transcription, Genetic


  • Chromatin
  • Histones
  • NF-kappa B
  • Nfkbia protein, mouse
  • Nucleosomes
  • Rela protein, mouse
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha
  • DNA