Functional Interactions between Retinoic Acid Receptor-related Orphan Nuclear Receptor (RORα) and the Retinoic Acid Receptors in the Regulation of the γF-Crystallin Promoter

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