Abstract

The daily rhythm in the activity of arylalkylamine N-acetyltransferase (AA-NAT) controls the rhythm in melatonin synthesis in the pineal gland. In the rat, transcriptional regulatory mechanisms play a major role in determining the observed pattern of AA-NAT gene expression. Remarkably, high levels of AA-NAT transcripts can only be detected in the night pineal; significant levels can also be found in the retina. To characterize the regulatory events that impinge upon the activity of the AA-NAT gene we embarked on the systematic analysis of the AA-NAT promoter. To this end we transfected several AA-NAT promoter derivative constructs to monitor reporter gene activity in both pineal and non-pineal primary cell cultures. Our studies revealed a cooperative arrangement between upstream promoter and downstream intronic regions which appear to contain most of the key elements necessary to ensure the proper spatio-temporal pattern of AA-NAT gene expression.

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