Analysis of a gene regulatory cascade mediating circadian rhythm in zebrafish.

Analysis of a gene regulatory cascade mediating circadian rhythm in zebrafish.
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DOI:
10.1371/journal.pcbi.1002940
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发表时间:
2013
影响因子:
4.3
通讯作者:
Yan J
Yan J
中科院分区:
生物学2区
文献类型:
--
作者:
Li Y;Li G;Wang H;Du J;Yan J

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In the study of circadian rhythms, it has been a puzzle how a limited number of circadian clock genes can control diverse aspects of physiology. Here we investigate circadian gene expression genome-wide using larval zebrafish as a model system. We made use of a spatial gene expression atlas to investigate the expression of circadian genes in various tissues and cell types. Comparison of genome-wide circadian gene expression data between zebrafish and mouse revealed a nearly anti-phase relationship and allowed us to detect novel evolutionarily conserved circadian genes in vertebrates. We identified three groups of zebrafish genes with distinct responses to light entrainment: fast light-induced genes, slow light-induced genes, and dark-induced genes. Our computational analysis of the circadian gene regulatory network revealed several transcription factors (TFs) involved in diverse aspects of circadian physiology through transcriptional cascade. Of these, microphthalmia-associated transcription factor a (mitfa), a dark-induced TF, mediates a circadian rhythm of melanin synthesis, which may be involved in zebrafish's adaptation to daily light cycling. Our study describes a systematic method to discover previously unidentified TFs involved in circadian physiology in complex organisms. For most animals whose lives are dependent on the sun, circadian clocks govern their daily behaviors and physiology. In different animals, novel functions under the circadian clock's control can evolve as adaptations to their specific environment. A zebrafish demonstrates a remarkably high level of interplay between external light and its internal circadian clock due to its transparent nature. In a genome-wide study, we identified a large number of circadian oscillating genes as well as genes whose expression is highly sensitive to the light or dark in zebrafish. Our computational analysis of gene regulatory networks revealed a number of transcription factors (TFs) that mediate novel circadian functions. We investigated one example in depth, a key TF that relays the control of the circadian clock to the enzymes synthesizing melanin in a dark-induced pathway thus causing the daily change of pigmentation in zebrafish. This dark-induced circadian melanogenesis can lead to an anticipatory change in zebrafish skin color allowing zebrafish to adapt to its environment. This mechanism allows zebrafish to better evade predators and effectively adjust its daily light-sensitivity in the pigment cells. Our study provides an excellent example of how the circadian clock is adapted in a specific organism to control its behavior, thus enabling evolutionary adaptation to the organism's ecological niche.
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