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- Title
Melatonin synthesis in retina: cAMP-dependent transcriptional regulation of chicken arylalkylamine N-acetyltransferase by a CRE-like sequence and a TTATT repeat motif in the proximal promoter.
- Authors
Haque, Rashidul; Chong, Nelson W.; Ali, Fatima; Chaurasia, Shyam S.; Sengupta, Trisha; Chun, Eugene; Howell, Jennifer C.; Klein, David C.; Michael Iuvone, P.
- Abstract
J. Neurochem. (2011) 119, 6-17. Abstract 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 ∼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 (TTATT8) 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 TTATT8 elements in the 484 bp proximal promoter interact to mediate cAMP-dependent transcriptional regulation of Aanat.
- Subjects
RETINA; ACETYLTRANSFERASES; MELATONIN; BIOSYNTHESIS; LUCIFERASES; FORSKOLIN
- Publication
Journal of Neurochemistry, 2011, Vol 119, Issue 1, p6
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2011.07397.x