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Homeobox-clock protein interaction in zebrafish. A
shared mechanism for pineal-specific and circadian gene
expression.
Appelbaum L, Anzulovich A, Baler R,
Gothilf Y.
Faculty of Life Sciences, Bar-Ilan University,
Ramat Gan 52900, Israel.
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.
PMID: 15657039 [PubMed - indexed for MEDLINE]
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