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

Functional differentiation of photoreceptor cells involves the expression of two sets of genes: those encoding the proteins of the phototransduction cascade and those encoding the enzymes of melatonin synthesis. The transcription factor Crx (cone-rod homeobox) plays a major role in the differentiation and maintenance of the photoreceptor phenotype. Previous studies have shown 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, hydroxyindol-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 recombinant Crx and bound a pineal/retina-specific protein showing DNA-binding characteristics similar to those of Crx. In transient transfection experiments, Crx transactivated transcription of a reporter gene from the chicken HIOMT promoter. Transactivation was observed even with a portion of promoter 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 the phototransduction cascade, but also by controlling the expression of the genes involved in melatonin synthesis.