Requirement for NF-κB in maintenance of molecular and behavioral circadian rhythms in mice.
(2018) Genes & Development — Vol. 32, n° 21-22, p. 1367-1379 (2018)
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Maury, Eléonore 
- Abstract
- The mammalian circadian clock is encoded by an autoregulatory transcription feedback loop that drives rhythmic behavior and gene expression in the brain and peripheral tissues. Transcriptomic analyses indicate cell type-specific effects of circadian cycles on rhythmic physiology, although how clock cycles respond to environmental stimuli remains incompletely understood. Here, we show that activation of the inducible transcription factor NF-κB in response to inflammatory stimuli leads to marked inhibition of clock repressors, including the , , and genes, within the negative limb. Furthermore, activation of NF-κB relocalizes the clock components CLOCK/BMAL1 genome-wide to sites convergent with those bound by NF-κB, marked by acetylated H3K27, and enriched in RNA polymerase II. Abrogation of NF-κB during adulthood alters the expression of clock repressors, disrupts clock-controlled gene cycles, and impairs rhythmic activity behavior, revealing a role for NF-κB in both unstimulated and activated conditions. Together, these data highlight NF-κB-mediated transcriptional repression of the clock feedback limb as a cause of circadian disruption in response to inflammation.
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Hong, H.-K., Maury, E., Ramsey, K. M., Perelis, M., Marcheva, B., Omura, C., Kobayashi, Y., Guttridge, D. C., Barish, G. D., & Bass, J. (2018). Requirement for NF-κB in maintenance of molecular and behavioral circadian rhythms in mice. Genes & Development, 32(21-22), 1367-1379. https://doi.org/10.1101/gad.319228.118 (Original work published 2018)