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

Hee Kyung Hong, Eleonore Maury, Kathryn Moynihan Ramsey, Mark Perelis, Biliana Marcheva, Chiaki Omura, Yumiko Kobayashi, Denis C. Guttridge, Grant D. Barish, Joseph Bass*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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 inre-sponse 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-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.

Original languageEnglish (US)
Pages (from-to)1367-1379
Number of pages13
JournalGenes and Development
Volume32
Issue number21-22
DOIs
StatePublished - Nov 1 2018

Keywords

  • Circadian
  • Genomics
  • High-fat diet
  • Inducible transcription
  • Inflammation
  • NF-κB

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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