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Zebrafish Serotonin-N-Acetyltransferase-2 Gene Regulation: Pineal-Restrictive Downstream Module Contains a Functional E-Box and Three Photoreceptor Conserved Elements

Department of Zoology (L.A., Y.G.), George S. Wise Faculty of Life Sciences 52900, Tel Aviv University, Tel Aviv 69978, Israel; Faculty of Life Sciences (L.A.,), Bar-Ilan University, Ramat Gan 52900, Israel; Laboratory of Molecular Genetics (R.T., I.B.D.) and Laboratory of Developmental Neurobiology (D.C.K.), National Institute of Child Health and Human Development, and Unit on Temporal Gene Expression (R.B.), Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Yoav Gothilf, Department of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 61390, Israel. E-mail: yoavg{at}tauex.tau.ac.il.

Pineal function is defined by a set of very narrowly expressed genes that encode proteins required for photoperiodic transduction and rhythmic melatonin secretion. One of these proteins is serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT), which controls the daily rhythm in melatonin production. Here, pineal-specific expression of the zebrafish aanat-2 (zfaanat-2) was studied using in vivo transient expression analyses of promoter-reporter constructs; this revealed that specificity is determined by two regions located 12 kb away from each other. One is the 5'-flanking region, and the other is a 257-bp sequence, located 6 kb downstream of the transcribed region. This 3'-sequence, designated pineal-restrictive downstream module (PRDM), has a dual function: enhancement of pineal expression and inhibition of extrapineal expression. The former is an autonomic property of PRDM whereas the later function requires interaction with the upstream regulatory region of zfaanat-2. Functional analyses of the PRDM sequence revealed that three photoreceptor conserved elements (TAATC) and a single perfect E-box (CACGTG) are crucial for the dual function of PRDM. These results indicate that pineal specificity of zfaanat-2 is determined by the dual functionality of the PRDM and the interaction between upstream regulatory region and downstream photoreceptor conserved elements and E-box element.

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