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H. Cheng, K.P. Mitton, H. Khanna, J. Friedman, A. Swaroop; Interaction Of Nr2e3, A Photoreceptor Specific Nuclear Receptor (pnr), And Rev–erb: Possible Role In Photoreceptor Gene Regulation And Differentiation . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5318.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: NR2E3, also known as photoreceptor specific nuclear receptor (PNR), plays a pivotal role in photoreceptor differentiation. Mutations in the human NR2E3 gene cause enhanced S–cone syndrome (ESCS), characterized by increased number of S–cone photoreceptors and retinal degeneration. Deletion of Nr2e3 in rd7 mice results in a similar phenotype. Our goal is to define the physiological function of NR2E3. Methods: We screened for potential interacting proteins of NR2E3 using yeast two hybrid assay with the human NR2E3 bait against a bovine retina library. The interaction results were confirmed by GST pull down assay, co–transfection and co–immunoprecipitation. Transfections were performed using luciferase reporter assays. Results: Rev–erb–alpha was shown to be one of the proteins interacting with NR2E3. Rev–erb–alpha, encoded by the opposite strand of the thyroid hormone receptor a gene, is a member of the nuclear receptor superfamily, implicated in regulating muscle differentiation, adipogenesis, and cerebellar development. Different deletions of NR2E3 and Rev–erb–alpha were constructed to find the possible interaction domain in both proteins. Various independent methods, including co–immunoprecipitation from bovine retinal extracts, confirmed this interaction. We have demonstrated that NR2E3 and Rev–erb–alpha could synergistically activate rhodopsin promoter. The rhodopsin promoter activity is further enhanced with the addition of NRL and CRX. Conclusions: Our results suggest that NR2E3 and Rev–erb–alpha regulate rod differentiation by modulating the expression of photoreceptor genes.
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