Defining the Independence of the Liver Circadian Clock

Kevin B. Koronowski, Kenichiro Kinouchi, Patrick Simon Welz, Jacob G. Smith, Valentina M. Zinna, Jiejun Shi, Muntaha Samad, Siwei Chen, Christophe N. Magnan, Jason M. Kinchen, Wei Li, Pierre Baldi, Salvador Aznar Benitah, Paolo Sassone-Corsi

Producción científica: Articlerevisión exhaustiva

193 Citas (Scopus)

Resumen

Mammals rely on a network of circadian clocks to control daily systemic metabolism and physiology. The central pacemaker in the suprachiasmatic nucleus (SCN) is considered hierarchically dominant over peripheral clocks, whose degree of independence, or tissue-level autonomy, has never been ascertained in vivo. Using arrhythmic Bmal1-null mice, we generated animals with reconstituted circadian expression of BMAL1 exclusively in the liver (Liver-RE). High-throughput transcriptomics and metabolomics show that the liver has independent circadian functions specific for metabolic processes such as the NAD+ salvage pathway and glycogen turnover. However, although BMAL1 occupies chromatin at most genomic targets in Liver-RE mice, circadian expression is restricted to ∼10% of normally rhythmic transcripts. Finally, rhythmic clock gene expression is lost in Liver-RE mice under constant darkness. Hence, full circadian function in the liver depends on signals emanating from other clocks, and light contributes to tissue-autonomous clock function. A autonomous branch of the liver circadian clock is independent from all other clocks yet still dependent on the light-dark cycle.

Idioma originalEnglish (US)
Páginas (desde-hasta)1448-1462.e14
PublicaciónCell
Volumen177
N.º6
DOI
EstadoPublished - may 30 2019
Publicado de forma externa

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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