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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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Related in: MedlinePlus

The circadian phase distributions of predicted targets of nine circadian TF motifs.The percentage of predicted targets within a certain phase is plotted against the circadian phase between 0 and 24 hours. The red bars indicate phase distributions of targets of circadian TFs, whereas the blue bars indicate the phase distribution of all ZCOGs as the background. Gray boxes show the enriched time windows of the targets (p<0.001). The matrix IDs corresponding to TFs were indicated in the parentheses (Table S7).
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pcbi-1002940-g003: The circadian phase distributions of predicted targets of nine circadian TF motifs.The percentage of predicted targets within a certain phase is plotted against the circadian phase between 0 and 24 hours. The red bars indicate phase distributions of targets of circadian TFs, whereas the blue bars indicate the phase distribution of all ZCOGs as the background. Gray boxes show the enriched time windows of the targets (p<0.001). The matrix IDs corresponding to TFs were indicated in the parentheses (Table S7).

Mentions: Because the circadian phases of ZCOGs show a bimodal distribution (Figure 1B), we divided ZCOGs into two groups, the first with peak times within CT22-CT10, and the second with peak times within CT10-CT22. In the first group, we identified E-BOX as the most enriched promoter motif (p value = 2.5×10−10, odds ratio = 2.3), while RRE is significantly enriched in promoters from the second group of genes (p value = 1.3×10−5, odds ratio = 2.0). This is consistent with observations in mouse except that the enriched phases are also shifted by about 10 hours following the same phase-shift of homologous TFs in zebrafish and mouse [5]. We then used a sliding window approach to identify the specific time window when the circadian phases of circadian TF targets are enriched (Table S7). In addition to E-BOX and RRE, we also observed that targets of ppargc1b, yy1a/b, atf/creb, hnf1a, foxo3b, and myog were enriched at a specific time window (p<0.001, Figure 3). There are varying delays between phases of TFs and enriched phases of their targets. Phases of tef, foxo3b, ppargc1b, and hnf1a are close to their targets, while arntl/clock, nfil3, yy1a, and myog are nearly anti-phase to their targets.


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)

The circadian phase distributions of predicted targets of nine circadian TF motifs.The percentage of predicted targets within a certain phase is plotted against the circadian phase between 0 and 24 hours. The red bars indicate phase distributions of targets of circadian TFs, whereas the blue bars indicate the phase distribution of all ZCOGs as the background. Gray boxes show the enriched time windows of the targets (p<0.001). The matrix IDs corresponding to TFs were indicated in the parentheses (Table S7).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585402&req=5

pcbi-1002940-g003: The circadian phase distributions of predicted targets of nine circadian TF motifs.The percentage of predicted targets within a certain phase is plotted against the circadian phase between 0 and 24 hours. The red bars indicate phase distributions of targets of circadian TFs, whereas the blue bars indicate the phase distribution of all ZCOGs as the background. Gray boxes show the enriched time windows of the targets (p<0.001). The matrix IDs corresponding to TFs were indicated in the parentheses (Table S7).
Mentions: Because the circadian phases of ZCOGs show a bimodal distribution (Figure 1B), we divided ZCOGs into two groups, the first with peak times within CT22-CT10, and the second with peak times within CT10-CT22. In the first group, we identified E-BOX as the most enriched promoter motif (p value = 2.5×10−10, odds ratio = 2.3), while RRE is significantly enriched in promoters from the second group of genes (p value = 1.3×10−5, odds ratio = 2.0). This is consistent with observations in mouse except that the enriched phases are also shifted by about 10 hours following the same phase-shift of homologous TFs in zebrafish and mouse [5]. We then used a sliding window approach to identify the specific time window when the circadian phases of circadian TF targets are enriched (Table S7). In addition to E-BOX and RRE, we also observed that targets of ppargc1b, yy1a/b, atf/creb, hnf1a, foxo3b, and myog were enriched at a specific time window (p<0.001, Figure 3). There are varying delays between phases of TFs and enriched phases of their targets. Phases of tef, foxo3b, ppargc1b, and hnf1a are close to their targets, while arntl/clock, nfil3, yy1a, and myog are nearly anti-phase to their targets.

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