Functional interactions between retinoic acid receptor-related orphan nuclear receptor (ROR alpha) and the retinoic acid receptors in the regulation of the gamma F-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.
Tini
M
M
Royal Victoria Hospital, Department of Biochemistry, McGill University, Montréal, Québec, Canada.
Fraser
R A
RA
Giguère
V
V
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D003459:Crystallins / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism
D003459:Crystallins; D017931:DNA Primers; D004275:DNA, Ribosomal; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors