Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression

TLDR

NF‑κB signaling is regulated by release from IκB, nuclear translocation, and a delayed negative‑feedback loop via IκBα transcription that generates oscillations, with target‑gene transcription depending on oscillation persistence. Single‑cell imaging and computational modeling showed asynchronous NF‑κB oscillations whose frequency decreases with increased IκBα transcription, indicating that the number, period, and amplitude of oscillations determine functional outcomes.

Abstract

Signaling by the transcription factor nuclear factor kappa B (NF-κB) involves its release from inhibitor kappa B (IκB) in the cytosol, followed by translocation into the nucleus. NF-κB regulation of IκBα transcription represents a delayed negative feedback loop that drives oscillations in NF-κB translocation. Single-cell time-lapse imaging and computational modeling of NF-κB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with increased IκBα transcription. Transcription of target genes depended on oscillation persistence, involving cycles of RelA phosphorylation and dephosphorylation. The functional consequences of NF-κB signaling may thus depend on number, period, and amplitude of oscillations.