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

The epigenome of macrophages can be reprogrammed by extracellular cues, but the extent to which different stimuli achieve this is unclear. Nuclear factor kappa B (NF-kappa B) 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-kappa B does so only in response to a subset of stimuli. This stimulus specificity depends on the temporal dynamics of NF-kappa B activity, in particular whether it is oscillatory or non-oscillatory. Non-oscillatory NF-kappa B 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.

Automated summary

The NF-κB transcription factor can reprogram the epigenome of macrophages by activating latent enhancers, but it only responds to certain stimuli, depending on the temporal dynamics of NF-κB activity. Non-oscillatory NF-κB can open chromatin and activate immune response genes by disrupting histone-DNA interactions, thereby modulating expression.