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

Li Y, Li G, Wang H, Du J, Yan J - PLoS Comput. Biol. (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
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.

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Global circadian gene expression in larval zebrafish.(A) Circadian expression of ZCOGs under both LD and DD conditions. High expression is indicated in red and low expression in green. The bar on the x-axis indicates light (white) and dark (black) in LD, and subjective day (gray) and subjective night (black) in DD. (B) Bimodal distribution of circadian phases of ZCOGs. (C) Circadian phases of homologous circadian genes between zebrafish and mouse. The mouse circadian genes are common circadian genes oscillating in at least six tissues from our previously constructed circadian gene databases [5]. Their circadian phases are averaged across these tissues. The regression line reflects the approximately 9-hour phase shift between zebrafish and mouse circadian genes. Duplicated genes in zebrafish are connected with vertical lines. The vertical bar indicates the zebrafish light/dark cycle (14 h∶10 h) and the horizontal bar indicates the mouse light/dark cycle (12 h∶12 h). (D) KEGG pathways enriched in specific time windows among ZCOGs.
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pcbi-1002940-g001: Global circadian gene expression in larval zebrafish.(A) Circadian expression of ZCOGs under both LD and DD conditions. High expression is indicated in red and low expression in green. The bar on the x-axis indicates light (white) and dark (black) in LD, and subjective day (gray) and subjective night (black) in DD. (B) Bimodal distribution of circadian phases of ZCOGs. (C) Circadian phases of homologous circadian genes between zebrafish and mouse. The mouse circadian genes are common circadian genes oscillating in at least six tissues from our previously constructed circadian gene databases [5]. Their circadian phases are averaged across these tissues. The regression line reflects the approximately 9-hour phase shift between zebrafish and mouse circadian genes. Duplicated genes in zebrafish are connected with vertical lines. The vertical bar indicates the zebrafish light/dark cycle (14 h∶10 h) and the horizontal bar indicates the mouse light/dark cycle (12 h∶12 h). (D) KEGG pathways enriched in specific time windows among ZCOGs.

Mentions: Circadian oscillating genes were identified using Fisher's g test, and their circadian phases were determined by fitting to cosine functions with shifting phases (Materials and Methods). We identified 2,856 circadian oscillating genes in both LD and DD conditions with an overall False Discovery Rate (FDR)≤5% (Table S1). These account for over 17% of expressed genes in larval zebrafish (Figure 1A). We thus refer to these zebrafish circadian oscillating genes in both LD and DD as “zebrafish circadian oscillating genes” (ZCOGs). The mean circadian phases under LD and DD are used to represent the circadian phases of ZCOGs. This dataset displays a prominent bimodal distribution with peaks at CT2 (Circadian Time 2; CT0 is lights-on and CT14 is lights-off) and CT16 corresponding to 2 hours after lights-on and lights-off respectively (Figure 1B).


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

Li Y, Li G, Wang H, Du J, Yan J - PLoS Comput. Biol. (2013)

Global circadian gene expression in larval zebrafish.(A) Circadian expression of ZCOGs under both LD and DD conditions. High expression is indicated in red and low expression in green. The bar on the x-axis indicates light (white) and dark (black) in LD, and subjective day (gray) and subjective night (black) in DD. (B) Bimodal distribution of circadian phases of ZCOGs. (C) Circadian phases of homologous circadian genes between zebrafish and mouse. The mouse circadian genes are common circadian genes oscillating in at least six tissues from our previously constructed circadian gene databases [5]. Their circadian phases are averaged across these tissues. The regression line reflects the approximately 9-hour phase shift between zebrafish and mouse circadian genes. Duplicated genes in zebrafish are connected with vertical lines. The vertical bar indicates the zebrafish light/dark cycle (14 h∶10 h) and the horizontal bar indicates the mouse light/dark cycle (12 h∶12 h). (D) KEGG pathways enriched in specific time windows among ZCOGs.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585402&req=5

pcbi-1002940-g001: Global circadian gene expression in larval zebrafish.(A) Circadian expression of ZCOGs under both LD and DD conditions. High expression is indicated in red and low expression in green. The bar on the x-axis indicates light (white) and dark (black) in LD, and subjective day (gray) and subjective night (black) in DD. (B) Bimodal distribution of circadian phases of ZCOGs. (C) Circadian phases of homologous circadian genes between zebrafish and mouse. The mouse circadian genes are common circadian genes oscillating in at least six tissues from our previously constructed circadian gene databases [5]. Their circadian phases are averaged across these tissues. The regression line reflects the approximately 9-hour phase shift between zebrafish and mouse circadian genes. Duplicated genes in zebrafish are connected with vertical lines. The vertical bar indicates the zebrafish light/dark cycle (14 h∶10 h) and the horizontal bar indicates the mouse light/dark cycle (12 h∶12 h). (D) KEGG pathways enriched in specific time windows among ZCOGs.
Mentions: Circadian oscillating genes were identified using Fisher's g test, and their circadian phases were determined by fitting to cosine functions with shifting phases (Materials and Methods). We identified 2,856 circadian oscillating genes in both LD and DD conditions with an overall False Discovery Rate (FDR)≤5% (Table S1). These account for over 17% of expressed genes in larval zebrafish (Figure 1A). We thus refer to these zebrafish circadian oscillating genes in both LD and DD as “zebrafish circadian oscillating genes” (ZCOGs). The mean circadian phases under LD and DD are used to represent the circadian phases of ZCOGs. This dataset displays a prominent bimodal distribution with peaks at CT2 (Circadian Time 2; CT0 is lights-on and CT14 is lights-off) and CT16 corresponding to 2 hours after lights-on and lights-off respectively (Figure 1B).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus