ZFIN ID: ZDB-PUB-050125-2
Homeobox-clock protein interaction in zebrafish: A shared mechanism for pineal-specific and circadian gene expression
Appelbaum, L. Anzulovich, A., Baler, R., and Gothilf, Y.
Date: 2005
Source: The Journal of biological chemistry   280(12): 11544-11551 (Journal)
Registered Authors: Gothilf, Yoav
Keywords: none
MeSH Terms:
  • Animals
  • Arylalkylamine N-Acetyltransferase/genetics*
  • Basic Helix-Loop-Helix Transcription Factors
  • CLOCK Proteins
  • Circadian Rhythm*
  • DNA-Binding Proteins/physiology
  • Dimerization
  • Gene Expression Regulation*
  • Genes, Homeobox
  • Homeodomain Proteins/physiology*
  • Otx Transcription Factors
  • Pineal Gland/metabolism
  • Trans-Activators/physiology*
  • Transcription Factors/physiology
  • Zebrafish
  • Zebrafish Proteins/physiology*
PubMed: 15657039 Full text @ J. Biol. Chem.
In non-mammalian vertebrates, the pineal gland is photoreceptive and contains an intrinsic circadian oscillator that drives rhythmic production and secretion of melatonin. These features require an accurate spatio-temporal expression of an array of specific genes in the pineal gland. Among these is the arylalkylamine-N-acetyltransferase (AANAT), a key enzyme in the melatonin production pathway. In zebrafish, pineal-specificity of zfaanat2 is determined by a region designated the pineal-restrictive downstream module (PRDM), which contains three photoreceptor conserved elements (PCEs) and an E-box, elements that are generally associated with photoreceptor-specific and rhythmic expression, respectively. Here, using in vivo and in vitro approaches, it was found that the PRDM PCEs and E-box mediate a synergistic effect of the photoreceptor-specific homeobox OTX5 and rhythmically-expressed clock protein heterodimer, BMAL/CLOCK, on zfaanat2 expression. Furthermore, the distance between the PCEs and E-box was found to be critical for PRDM function, suggesting a possible physical feature of this synergistic interaction. OTX5 - BMAL/CLOCK may act through this mechanism to simultaneously control pineal-specific and rhythmic expression of zfaanat2 and possibly also other pineal and retinal genes.