[PDF][PDF] A functional genomics strategy reveals Rora as a component of the mammalian circadian clock

TK Sato, S Panda, LJ Miraglia, TM Reyes, RD Rudic… - Neuron, 2004 - cell.com
TK Sato, S Panda, LJ Miraglia, TM Reyes, RD Rudic, P McNamara, KA Naik, GA FitzGerald
Neuron, 2004cell.com
The mammalian circadian clock plays an integral role in timing rhythmic physiology and
behavior, such as locomotor activity, with anticipated daily environmental changes. The
master oscillator resides within the suprachiasmatic nucleus (SCN), which can maintain
circadian rhythms in the absence of synchronizing light input. Here, we describe a genomics-
based approach to identify circadian activators of Bmal1, itself a key transcriptional activator
that is necessary for core oscillator function. Using cell-based functional assays, as well as …
Abstract
The mammalian circadian clock plays an integral role in timing rhythmic physiology and behavior, such as locomotor activity, with anticipated daily environmental changes. The master oscillator resides within the suprachiasmatic nucleus (SCN), which can maintain circadian rhythms in the absence of synchronizing light input. Here, we describe a genomics-based approach to identify circadian activators of Bmal1, itself a key transcriptional activator that is necessary for core oscillator function. Using cell-based functional assays, as well as behavioral and molecular analyses, we identified Rora as an activator of Bmal1 transcription within the SCN. Rora is required for normal Bmal1 expression and consolidation of daily locomotor activity and is regulated by the core clock in the SCN. These results suggest that opposing activities of the orphan nuclear receptors Rora and Rev-erb α, which represses Bmal1 expression, are important in the maintenance of circadian clock function.
cell.com