Clock-dependent and independent transcriptional control of the two isoforms from the mouse Rorgamma 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 Rorgammaisoforms (Rorgamma and Rorgammat) and characterize the molecular mechanisms underlying their tissue-specific expression. The expression of Rorgamma isoforms was assessed in mouse liver, muscle, thymus and testis throughout 24 h using quantitative RT-PCR. Although the expression of Rorgamma was rhythmic in the liver and thymus, it was constitutively expressed in muscle and testis. In contrast, the expression of Rorgammat was constitutive in all four tissues. Furthermore, rhythmic expression of Rorgamma was impaired in Clock mutant mice whereas the mutation had no effect on Rorgammat expression. In line with these findings, luciferase assays revealed that transcription of the Rorgamma promoter is clock-controlled whereas that of Rorgammat promoter is essentially clock-independent. Our results provide insights into the molecular mechanisms that lead to differential expression of Rorgamma and Rorgammat and are suggestive of a framework that might account for tissue-specific circadian regulation.