Clock-dependent and independent transcriptional control of the two isoforms from the mouse Rorγ gene

Accumulating evidence indicate that molecular mechanisms generating circadian rhythms display some degree of tissue-specificity. More specifically, distinct patterns of expression for nuclear receptors of the ROR family indicate that the transcriptional control of the clock gene Bmal1 differs among tissues. This study aims to investigate the expression of Ror gamma isoforms (Ror gamma and Ror gamma t) and characterize the molecular mechanisms underlying their tissue-specific expression. The expression of Ror gamma isoforms was assessed in mouse liver, muscle, thymus and testis throughout 24 h using quantitative RT-PCR. Although the expression of Ror gamma was rhythmic in the liver and thymus, it was constitutively expressed in muscle and testis. In contrast, the expression of Ror gamma t was constitutive in all four tissues. Furthermore, rhythmic expression of Ror gamma was impaired in Clock mutant mice whereas the mutation had no effect on Ror gamma t expression. In line with these findings, luciferase assays revealed that transcription of the Ror gamma promoter is clock-controlled whereas that of Ror gamma t promoter is essentially clock-independent. Our results provide insights into the molecular mechanisms that lead to differential expression of Ror gamma and Ror gamma t and are suggestive of a framework that might account for tissue-specific circadian regulation.