Transcriptional regulation of the chicken hydroxyindole-O-methyltransferase gene by the cone-rod homeobox-containing protein

Functional differentiation of photoreceptor cells involves the expression o f two sets of genes: those encoding the proteins of the phototransduction c ascade and those encoding the enzymes of melatonin synthesis. The transcrip tion factor Crx (cone-rod homeobox) plays a major role in the differentiati on and maintenance of the photoreceptor phenotype. Previous studies have sh own that this effect of Crx is correlated with its ability to transactivate several genes of the phototransduction cascade. Here, we show that Crx can also act on the gene encoding the melatonin-synthesizing enzyme, hydroxyin dol-O-methyltransferase (HIOMT, EC 2.1.1.4). Three of the six putative Crx- binding sites found in the chicken HIOMT promoter interact directly with re combinant Crx and bound a pineal/retina-specific protein showing DNA-bindin g characteristics similar to those of Crx. In transient transfection experi ments, Crx transactivated transcription of a reporter gene from the chicken HIOMT promoter. Transactivation was observed even with a portion of promot er carrying only one Crx-binding site and it was abolished by a mutation in this cis-regulatory element. These data indicate that Crx may participate in photoreceptor cell differentiation, not only by acting on the genes of t he phototransduction cascade, but also by controlling the expression of the genes involved in melatonin synthesis.