Journal
JOURNAL OF NEUROCHEMISTRY
Volume 119, Issue 1, Pages 6-17Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1471-4159.2011.07397.x
Keywords
Aanat; AP1; CRE; CREB; melatonin; retina
Categories
Funding
- NIH [R01EY004864, P30EY006360]
- Eunice Shriver Kennedy National Institute of Child Health and Human Development
- Research to Prevent Blindness (RPB)
- BBSRC UK [G18273]
- Biotechnology and Biological Sciences Research Council [G18273] Funding Source: researchfish
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Arylalkylamine N-acetyltransferase (AANAT) is the key regulatory enzyme controlling the daily rhythm of melatonin biosynthesis. In chicken retinal photoreceptor cells, Aanat transcription and AANAT activity are regulated in part by cAMP-dependent mechanisms. The purpose of this study was to identify regulatory elements within the chicken Aanat promoter responsible for cAMP-dependent induction. Photoreceptor-enriched retinal cell cultures were transfected with a luciferase reporter construct containing up to 4 kb of 5'-flanking region and the first exon of Aanat. Forskolin treatment stimulated luciferase activity driven by the similar to 4 kb promoter construct and by all 5'-deletion constructs except the smallest, Aanat (-217 to +120)luc. Maximal basal and forskolin-stimulated expression levels were generated by the Aanat (-484 to +120)luc construct. This construct lacks a canonical cyclic AMP-response element (CRE), but contains two other potentially important elements in its sequence: an eight times TTATT repeat (TTATT(8)) and a CRE-like sequence. Electrophoretic mobility shift assays, luciferase reporter assays, chromatin immunoprecipitation, and siRNA experiments provide evidence that these elements bind c-Fos, JunD, and CREB to enhance basal and forskolin-stimulated Aanat transcription. We propose that the CRE-like sequence and TTATT(8) elements in the 484 bp proximal promoter interact to mediate cAMP-dependent transcriptional regulation of Aanat.
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