Abstract
Advances in transcriptional profiling methods have allowed for the simultaneous measurement of the transcriptome of mammals. We have applied these tools to the study of the mammalian circadian clock, which governs rhythmic physiology and behavior, such as locomotor activity, to anticipated daily changes in the environment. Transcriptional profiling of the suprachiasmatic nucleus of the hypothalamus, the site of the master circadian oscillator, as well as peripheral clocks resident in the liver, aorta, and kidney, revealed a subset of genes that cycle in most tissues. Having observed that several of these ‘pan-cycling’ genes were known clock components, we used a cell-based functional assay to identify those that may regulate Bmal1 transcription within the SCN. This work revealed that Rora is required for normal Bmal1 expression, as well as for normal consolidation of daily locomotor activity. Finally, we show that Rora is itself regulated by the core clock in the SCN. These results suggest that opposing activities of the orphan nuclear receptors Rora and Rev-erb-alpha, which represses Bmal1 expression, are important in the regulation of the circadian clock. [Jpn J Physiol 55 Suppl:S54 (2005)]
