Analysis of a gene regulatory cascade mediating circadian rhythm in zebrafish

PLoS Comput Biol. 2013;9(2):e1002940. doi: 10.1371/journal.pcbi.1002940. Epub 2013 Feb 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Circadian Rhythm Signaling Peptides and Proteins / genetics
  • Circadian Rhythm Signaling Peptides and Proteins / metabolism
  • Circadian Rhythm Signaling Peptides and Proteins / physiology*
  • Databases, Protein
  • Gene Regulatory Networks / genetics
  • Gene Regulatory Networks / physiology*
  • Larva
  • Light
  • Melanins / chemistry
  • Melanins / metabolism
  • Mice
  • Transcription Factors
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zebrafish Proteins / physiology*


  • Circadian Rhythm Signaling Peptides and Proteins
  • Melanins
  • Transcription Factors
  • Zebrafish Proteins

Grant support

This research was supported by SIBS dry-wet collaboration grant. Jun Yan is an Independent Research Group leader supported by both Chinese Academy of Sciences and German Max-Planck Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.