title: Homeobox-clock protein interaction in zebrafish. A shared mechanism for pineal-specific and circadian gene expression.
abstract: 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 spatiotemporal expression of an array of specific genes in the pineal gland. Among these is the arylalkylamine N-acetyltransferase, 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, by using in vivo and in vitro approaches, it was found that the PCEs and E-box of the PRDM 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 the 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.
authors.affiliation: Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Appelbaum
authors.forename: Ana
authors.initials: A
authors.lastname: Anzulovich
authors.forename: Ruben
authors.initials: R
authors.lastname: Baler
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gothilf
mesh_terms: D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D002940:Circadian Rhythm; D004268:DNA-Binding Proteins / Q000502:physiology; D019281:Dimerization; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000502:physiology*; D051857:Otx Transcription Factors; D010870:Pineal Gland / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D047068:Arylalkylamine N-Acetyltransferase; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C413467:Otx5 protein, zebrafish