System-Driven and Oscillator-Dependent Circadian Transcription in Mice with a Conditionally Active Liver Clock

The mammalian circadian timing system consists of a master pacemaker in neurons of the suprachiasmatic nucleus (SCN) and clocks of a similar molecular makeup in most peripheral body cells. Peripheral oscillators are self-sustained and cell autonomous, but they have to be synchronized by the SCN to ensure phase coherence within the organism. In principle, the rhythmic expression of genes in peripheral organs could thus be driven not only by local oscillators, but also by circadian systemic signals. To discriminate between these mechanisms, we engineered a mouse strain with a conditionally active liver clock, in which REV-ERBalpha represses the transcription of the essential core clock gene Bmal1 in a…

• NS
  National Science Foundation
• HH
  Howard Hughes Medical Institute
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
• BS
  Bonizzi-Theler Stiftung