Molecular oscillation of Per1 and Per2 genes in the rodent brain: an in situ hybridization and molecular biological study.

The circadian rhythm is originally generated by a transcription-translation based oscillatory loop where Per1 and Per2 genes locate in its central. In the rat brain, rhythmic expressions of Per1 and Per2 were observed not only in neurons of the hypothalamic suprachiasmatic nucleus (SCN) but also in those of non-SCN regions including the cerebral cortex. The E-box enhancer elements possible to regulate transcription of Per1 and Per2 genes were highly conserved in rats and mice. When E-box-activating transcription factors, CLOCK and BMAL1, were coexpressed, each of both proteins showed two molecular forms. The presence of these higher molecular weight forms seems to be correlated with the E-box mediated transcription activation. This mechanism might not be involved in the PER2 mediated suppression of E-box, since adding PER2 did not change the content of the higher molecular forms of CLOCK and BMAL1.