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

    Cell, 05/2019, Letnik: 177, Številka: 6
    Journal Article

    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. Display omitted •The liver clock oscillates in the absence of all other clocks in vivo•Only ∼20% of hepatic rhythms are autonomous despite recruitment of BMAL1 to chromatin•The liver clock is sufficient for oscillation of glycogen and NAD+ salvage metabolism•These autonomous oscillations depend on the light-dark cycle A autonomous branch of the liver circadian clock is independent from all other clocks yet still dependent on the light-dark cycle.