Requirement for NF-{kappa}B in maintenance of molecular and behavioral circadian rhythms in mice [Research Papers]
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-B in response to inflammatory stimuli leads to marked inhibition of clock repressors, including the Period, Cryptochrome, and Rev-erb genes, within the negative limb. Furthermore, activation of NF-B relocalizes the clock components CLOCK/BMAL1 genome-wide to sites convergent with those bound by NF-B, marked by acetylated H3K27, and enriched in RNA polymerase II. Abrogation of NF-B during adulthood alters the expression of clock repressors, disrupts clock-controlled gene cycles, and impairs rhythmic activity behavior, revealing a role for NF-B in both unstimulated and activated conditions. Together, these data highlight NF-B-mediated transcriptional repression of the clock feedback limb as a cause of circadian disruption in response to inflammation.
Source: Genes and Development - Category: Genetics & Stem Cells Authors: Hong, H.-K., Maury, E., Ramsey, K. M., Perelis, M., Marcheva, B., Omura, C., Kobayashi, Y., Guttridge, D. C., Barish, G. D., Bass, J. Tags: Research Papers Source Type: research