The light-induced transcriptome of the zebrafish pineal gland reveals complex regulation of the circadian clockwork by light

Zohar Ben-Moshe, Shahar Alon, Philipp Mracek, Lior Faigenbloom, Adi Tovin, Gad D. Vatine, Eli Eisenberg, Nicholas S. Foulkes, Yoav Gothilf

Research output: Contribution to journalArticlepeer-review

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 lightinduced in the pineal gland. Four of these genes, encoding the transcription factors dec1, reverbb1, e4bp4-5 and e4bp4-6, differentially affected clockand 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 30UTR target site, and importantly, to regulate the rhythmic mRNA levels of aanat2, the key enzyme in melatonin synthesis. Together, this genomewide approach and functional characterization of light-induced factors indicate a multi-level regulation of the circadian clockwork by light.

Original languageEnglish
Pages (from-to)3750-3767
Number of pages18
JournalNucleic Acids Research
Volume42
Issue number6
DOIs
StatePublished - Apr 2014

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