NF-κB oscillations translate into functionally related patterns of gene expression

Area of Science:

• Cellular dynamics
• Molecular biology
• Systems biology

Background:

• Transcription factors (TFs) like NF-κB oscillate between cellular compartments.
• The biological significance of NF-κB oscillations, crucial in inflammation and cancer, is not fully understood.
• Previous studies suggested sustained NF-κB oscillations can be entrained by external stimuli.

Purpose of the Study:

• To investigate the oscillatory behavior of NF-κB in GFP-p65 knock-in cells.
• To determine how NF-κB oscillations synchronize with external periodic perturbations.
• To analyze the resulting patterns of NF-κB-controlled gene transcription.

Main Methods:

• Utilized GFP-p65 knock-in cells to track NF-κB dynamics.
• Applied periodic external perturbations to study entrainment and synchronization.
• Analyzed mRNA levels of NF-κB-controlled genes under synchronous dynamics.

Main Results:

• NF-κB exhibited damped oscillatory behavior, synchronizing with external perturbations without memory.
• Transcription of NF-κB-controlled genes also oscillated.
• Mature transcript levels displayed three patterns: fast accumulation, slow accumulation, and oscillation with stimulus resetting.

Conclusions:

• NF-κB oscillatory dynamics can be entrained by external signals.
• Oscillating transcripts, like chemokine and chemokine receptor mRNAs, reset with each stimulus, indicating a lack of memory.
• TF oscillatory dynamics may serve to segment time, providing temporal windows for cellular decision-making.