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Nucleic Acids Res. 2014 Apr;42(6):3750-67. doi: 10.1093/nar/gkt1359. Epub 2014 Jan 13.

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

Author information

1
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.

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.

PMID:
24423866
PMCID:
PMC3973289
DOI:
10.1093/nar/gkt1359
[Indexed for MEDLINE]
Free PMC Article
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