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N. J. Mollema, A. M. Nystuen, N. B. Haider; The Nuclear Receptor Gene Nr1d1 Functions With Nr2e3 to Regulate the Expression of Photoreceptor-Specific Genes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):486.
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The nuclear receptor Nr2e3 is essential for retinal development and mutations in Nr2e3 result in retinal degeneration. Nr1d1 was recently identified as a cofactor for Nr2e3 however its function in the retina remains unknown. The purpose of this study is to determine the role of the nuclear receptor Nr1d1 in the developing and mature retina and identify the common transcriptional networks regulated by Nr2e3 and Nr1d1 in photoreceptor cells.
Tissues were collected at embryonic (E) and postnatal (P) time points of E10, E12, E14, E16, E18, P2, P6, and adult to determine the temporal and spatial expression profile of Nr1d1. QRT-PCR and immunohistochemistry were performed to determine the expression of Nr1d1 mRNA and protein. We performed in vivo chromatin immunoprecipitation (ChIP) using E18 and P30 B6 and rd7 mouse retinas to determine what genes are co-targeted by Nr2e3 and Nr1d1. In vitro assays were conducted to confirm that Nr1d1 regulates the expression of genes that were positive by ChIP.
Nr1d1 is expressed in the developing and adult retina. During development NR1D1 co-localizes with NR2E3 in retinal progenitor cells. In the adult, NR1D1 protein localizes to cones and ganglion cells. Nr1d1 and Nr2e3, in the developing and mature retinas, commonly regulated several gene targets.
Nr1d1, known also as Rev-erb alpha, has been well studied as a regulator of circadian rhythm. This study uncovers a novel role for Nr1d1 in the regulation of retinal specific genes. Nr1d1 regulates gene expression in developing and mature photoreceptor cells. Several genes identified in this study are associated with human retinal diseases and are known to function in photoreceptor development and maintenance.
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