title: The light-induced transcriptome of the zebrafish pineal gland reveals complex regulation of the circadian clockwork by light.
abstract: Light constitutes a primary signal whereby endogenous circadian clocks are synchronized ('entrained') with the day/night cycle. The molecular mechanisms underlying this vital process are known to require gene activation, yet are incompletely understood. Here, the light-induced transcriptome in the zebrafish central clock organ, the pineal gland, was characterized by messenger RNA (mRNA) sequencing (mRNA-seq) and microarray analyses, resulting in the identification of multiple light-induced mRNAs. Interestingly, a considerable portion of the molecular clock (14 genes) is light-induced in the pineal gland. Four of these genes, encoding the transcription factors dec1, reverbb1, e4bp4-5 and e4bp4-6, differentially affected clock- and light-regulated promoter activation, suggesting that light-input is conveyed to the core clock machinery via diverse mechanisms. Moreover, we show that dec1, as well as the core clock gene per2, is essential for light-entrainment of rhythmic locomotor activity in zebrafish larvae. Additionally, we used microRNA (miRNA) sequencing (miR-seq) and identified pineal-enhanced and light-induced miRNAs. One such miRNA, miR-183, is shown to downregulate e4bp4-6 mRNA through a 3'UTR target site, and importantly, to regulate the rhythmic mRNA levels of aanat2, the key enzyme in melatonin synthesis. Together, this genome-wide approach and functional characterization of light-induced factors indicate a multi-level regulation of the circadian clockwork by light.
authors.affiliation: George S. Wise Faculty of Life Sciences, Department of Neurobiology, Tel-Aviv University, Tel-Aviv 69978, Israel, Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv 69978, Israel, Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen 76344, Germany and Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Ben-Moshe
authors.forename: Shahar
authors.initials: S
authors.lastname: Alon
authors.forename: Philipp
authors.initials: P
authors.lastname: Mracek
authors.forename: Lior
authors.initials: L
authors.lastname: Faigenbloom
authors.forename: Adi
authors.initials: A
authors.lastname: Tovin
authors.forename: Gad D
authors.initials: GD
authors.lastname: Vatine
authors.forename: Eli
authors.initials: E
authors.lastname: Eisenberg
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Foulkes
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gothilf
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D057906:Circadian Clocks / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D008124:Locomotion; D053858:Metabolic Networks and Pathways / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism; D010870:Pineal Gland / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000528:radiation effects*; D059467:Transcriptome / Q000528:radiation effects*; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C000588976:MIRN183 microRNA, zebrafish; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors