Mechanism of pineal-specific gene expression: The role of E-box and photoreceptor conserved elements

Photoreceptor cells of the pineal gland express distinct sets of proteins dedicated to photoreception, phototransduction and to rhythmic melatonin production. This review discusses the function of key regulatory sequences and nuclear factors that determine tissue-restricted expression of photoreceptor genes, specifically, the photoreceptor conserved element (PCE) and the E-box and their cognate binding proteins. Recent research in zebrafish revealed that PCE and E-box mediate the action of OTX5 and BMAL/CLOCK, respectively. These transcription factors drive enhanced expression of serotonin-N-acetyltransferase-2 (aanat2) in the pineal gland by synergistic interaction. Extensive research of other photoreceptor-specific genes suggested that the presence of several PCEs along with additional sequence elements is required to drive enhanced tissue-specific expression of these genes. Therefore, the mechanism identified for zebrafish aanat2, or at least part of it, may apply to other photoreceptor-specific genes in zebrafish and other species.