Dataset Information

Requirement for NF-?B in maintenance of molecular and behavioral circadian rhythms in mice.

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-?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.

SUBMITTER: Hong HK

PROVIDER: S-EPMC6217733 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Requirement for NF-κB in maintenance of molecular and behavioral circadian rhythms in mice.

Hong Hee-Kyung HK Maury Eleonore E Ramsey Kathryn Moynihan KM Perelis Mark M Marcheva Biliana B Omura Chiaki C Kobayashi Yumiko Y Guttridge Denis C DC Barish Grant D GD Bass Joseph J

Genes & development 20181026 21-22

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 i ...[more]

PMID: 30366905

Similar Datasets

Project description:Circadian rhythms are internal processes repeating approximately every 24 hours in living organisms. The dominant circadian pacemaker is synchronized to the environmental light-dark cycle. Other circadian pacemakers, which can have noncanonical circadian mechanisms, are revealed by arousing stimuli, such as scheduled feeding, palatable meals and running wheel access, or methamphetamine administration. Organisms also have ultradian rhythms, which have periods shorter than circadian rhythms. However, the biological mechanism, origin, and functional significance of ultradian rhythms are not well-elucidated. The dominant circadian rhythm often masks ultradian rhythms; therefore, we disabled the canonical circadian clock of mice by knocking out Per1/2/3 genes, where Per1 and Per2 are essential components of the mammalian light-sensitive circadian mechanism. Furthermore, we recorded wheel-running activity every minute under constant darkness for 272 days. We then investigated rhythmic components in the absence of external influences, applying unique multiscale time-resolved methods to analyze the oscillatory dynamics with time-varying frequencies. We found four rhythmic components with periods of ∼17 h, ∼8 h, ∼4 h, and ∼20 min. When the ∼17-h rhythm was prominent, the ∼8-h rhythm was of low amplitude. This phenomenon occurred periodically approximately every 2-3 weeks. We found that the ∼4-h and ∼20-min rhythms were harmonics of the ∼8-h rhythm. Coupling analysis of the ridge-extracted instantaneous frequencies revealed strong and stable phase coupling from the slower oscillations (∼17, ∼8, and ∼4 h) to the faster oscillations (∼20 min), and weak and less stable phase coupling in the reverse direction and between the slower oscillations. Together, this study elucidated the relationship between the oscillators in the absence of the canonical circadian clock, which is critical for understanding their functional significance. These studies are essential as disruption of circadian rhythms contributes to diseases, such as cancer and obesity, as well as mood disorders.

Dataset Information

Requirement for NF-?B in maintenance of molecular and behavioral circadian rhythms in mice.

Publications

Requirement for NF-κB in maintenance of molecular and behavioral circadian rhythms in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets