TRYPTOPHAN-HYDROXYLASE EXPRESSION IS REGULATED BY A CIRCADIAN CLOCK IN XENOPUS-LAEVIS RETINA

A circadian clock has been localized to the photoreceptor layer in the Xenopus laevis retina. This clock controls the rhythmic synthesis of melatonin, which results in elevated levels during the night and low l evels during the day. The rate-limiting enzyme in melatonin synthesis in Xenopus laevis retina is tryptophan hydroxylase. A cDNA clone codin g for Xenopus tryptophan hydroxylase was isolated, characterized, and used as a probe for analysis of tryptophan hydroxylase mRNA expression . Northern blot analyses of total retinal RNA show that the tryptophan hydroxylase message levels are low in the day and higher at night. Th e expression of tryptophan hydroxylase mRNA is under circadian control because rhythmic changes are also seen in constant darkness, with ele vated levels during the subjective night. Nuclear run-on analysis duri ng the first subjective day in constant darkness revealed that transcr iption initiation is low early in the day and increases throughout the day. Our observations suggest that the circadian clock modulates tryp tophan hydroxylase gene expression. An understanding of how the circad ian clock controls tryptophan hydroxylase expression may lead to a cle arer understanding of the melatonin biosynthetic pathway, and possibly the clock itself.