Functional interactions between retinoic acid receptor-related orphan nuclear receptor (RORα) and the retinoic acid receptors in the regulation of the γF-crystallin promoter

Abstract

We have previously demonstrated that an everted repeat of the hexamer PuGGTCA located within the γF-crystallin promoter mediates activation of the routine γF-crystallin gene by retinoic acid and thyroid hormone receptors. Here, we show that the recently identified retinoic acid receptor-related orphan nuclear receptor (RORα) is expressed in the murine lens and activates the γF-crystallin promoter. In contrast to the retinoic acid and thyroid hormone receptors, activation of the γF-crystallin promoter by RORα requires binding to the single 3' half-site and spacer sequences of γF- crystallin hormone response element (γF-HRE). We further demonstrate that RORα-dependent activation is repressed by the competitive binding of retinoic acid receptor/retinoid X receptor heterodimers to the γF-HRE in the absence of all-trans-retinoic acid. These studies suggest that the interplay of retinoid receptors and RORα on the γF-HRE may constitute an important mechanism regulating γF-crystallin gene expression in the murine lens.