Timing cues epigenomic reprogramming Different temporal dynamics of activation of the transcription factor nuclear factor κB (NF-κB) can influence the inflammatory response of activated macrophages. Cheng et al. report a mechanism by which oscillatory and sustained NF-κB signaling may produce distinct transcriptional responses (see the Perspective by Nandagopal et al. ). Oscillatory activation of NF-κB activated poised enhancers to transcribe inflammatory genes in mouse macrophages. However, sustained activation of NF-κB produced in cells activated by other stimuli acted on the epigenome. These stimuli relieved chromatin silencing at enhancers and enabled regulation of additional genes. Science , abc0269, this issue p. 1349 ; see also abj2040, p. 1263