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Preparing macrophages for the future

Temporal dynamics of a key immune transcription factor shape the epigenome and future cell responses Cells live in complex environments and must respond appropriately to extracellular signals. Such responses often involve regulating the expression of hundreds of genes through transcription factors (TFs). Many TFs are activated by multiple signals and regulate the expression of distinct genes in response to each. How extracellular information is “encoded” in TF activity and subsequently “decoded” to orchestrate gene expression is a fundamental question in biology. Intriguingly, some TFs such as nuclear factor κB (NF-κB) and p53 encode signaling information in their temporal dynamics (1). Studies have shown that signaling dynamics can be used to control the induced expression levels (2), types (3), or ratios (4) of genes. On page 1349 of this issue, Cheng et al. (5) report a previously unknown role for TF dynamics: They show that NF-κB dynamics not only control how genes respond in the present but also reconfigure the cell to control gene expression in response to future stimulation.