In mammals, circadian rhythms are generated by transcriptional-translational feedback loops consisting of a set of clock genes and their protein products. Among them, Bmal1 is a critical clock gene in generating and maintaining circadian rhythms. Moreover, orphan nuclear receptors REV-ERBs and RORs were known to respectively repress and activate Bmal1 transcription. In our study, we further demonstrated that: (1) REV-ERBalpha might be the main regulator in maintaining Bmal1 oscillation in thymus. (2) Rorgamma mRNA is constant in muscle and testis, and rhythmic in liver, while Rorgammat mRNA is only expressed in thymus, at constant levels. Moreover, the expressions of these two Rorgamma isoforms are affected in Clock mutant mice in a distinct way. (3) RORgamma and RORgammat can activate Bmal1 transcription at a similar level. (4) Rorgamma is a clock-controlled gene. Altogether, our results suggest that the crucial role of REV-ERBs and RORs in peripheral clocks. Furthermore, our work highlights functional differences among mammalian peripheral clocks, which provides important insights into the complexity of the circadian system.

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