Nuclear receptor Rev-erb alpha (Nr1d1) functions in concert with Nr2e3 to regulate transcriptional networks in the retina

The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated by genes such as nuclear hormone receptors. The nuclear hormone receptor gene Rev-erb alpha/Nr1d1...

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Veröffentlicht in:PloS one 2011-03, Vol.6 (3), p.e17494-e17494
Hauptverfasser: Mollema, Nissa J, Yuan, Yang, Jelcick, Austin S, Sachs, Andrew J, von Alpen, Désirée, Schorderet, Daniel, Escher, Pascal, Haider, Neena B
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creator Mollema, Nissa J
Yuan, Yang
Jelcick, Austin S
Sachs, Andrew J
von Alpen, Désirée
Schorderet, Daniel
Escher, Pascal
Haider, Neena B
description The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated by genes such as nuclear hormone receptors. The nuclear hormone receptor gene Rev-erb alpha/Nr1d1 has been widely studied for its role in the circadian cycle and cell metabolism, however its role in the retina is unknown. In order to understand the role of Rev-erb alpha/Nr1d1 in the retina, we evaluated the effects of loss of Nr1d1 to the developing retina and its co-regulation with the photoreceptor-specific nuclear receptor gene Nr2e3 in the developing and mature retina. Knock-down of Nr1d1 expression in the developing retina results in pan-retinal spotting and reduced retinal function by electroretinogram. Our studies show that NR1D1 protein is co-expressed with NR2E3 in the outer neuroblastic layer of the developing mouse retina. In the adult retina, NR1D1 is expressed in the ganglion cell layer and is co-expressed with NR2E3 in the outer nuclear layer, within rods and cones. Several genes co-targeted by NR2E3 and NR1D1 were identified that include: Nr2c1, Recoverin, Rgr, Rarres2, Pde8a, and Nupr1. We examined the cyclic expression of Nr1d1 and Nr2e3 over a twenty-four hour period and observed that both nuclear receptors cycle in a similar manner. Taken together, these studies reveal a novel role for Nr1d1, in conjunction with its cofactor Nr2e3, in regulating transcriptional networks critical for photoreceptor development and function.
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The transcriptional networks directing these processes are regulated by genes such as nuclear hormone receptors. The nuclear hormone receptor gene Rev-erb alpha/Nr1d1 has been widely studied for its role in the circadian cycle and cell metabolism, however its role in the retina is unknown. In order to understand the role of Rev-erb alpha/Nr1d1 in the retina, we evaluated the effects of loss of Nr1d1 to the developing retina and its co-regulation with the photoreceptor-specific nuclear receptor gene Nr2e3 in the developing and mature retina. Knock-down of Nr1d1 expression in the developing retina results in pan-retinal spotting and reduced retinal function by electroretinogram. Our studies show that NR1D1 protein is co-expressed with NR2E3 in the outer neuroblastic layer of the developing mouse retina. In the adult retina, NR1D1 is expressed in the ganglion cell layer and is co-expressed with NR2E3 in the outer nuclear layer, within rods and cones. Several genes co-targeted by NR2E3 and NR1D1 were identified that include: Nr2c1, Recoverin, Rgr, Rarres2, Pde8a, and Nupr1. We examined the cyclic expression of Nr1d1 and Nr2e3 over a twenty-four hour period and observed that both nuclear receptors cycle in a similar manner. Taken together, these studies reveal a novel role for Nr1d1, in conjunction with its cofactor Nr2e3, in regulating transcriptional networks critical for photoreceptor development and function.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21408158</pmid><doi>10.1371/journal.pone.0017494</doi><oa>free_for_read</oa></addata></record>
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subjects Aging - metabolism
Aging - radiation effects
Animals
Biology
Cell Count
Circadian rhythms
Cofactors
Concerts
Cones
Electroretinograms
Enhancer Elements, Genetic - genetics
Gene expression
Gene Regulatory Networks - genetics
Genes
Genetic aspects
Genetic research
Genetics
Injections
Ligands
Light
Light Signal Transduction - genetics
Light Signal Transduction - radiation effects
Metabolism
Mice
Musculoskeletal system
Mutation
Networks
Nuclear Receptor Subfamily 1, Group D, Member 1 - metabolism
Nuclear receptors
Organ Specificity - radiation effects
Orphan Nuclear Receptors - metabolism
Photoreceptors
Physiological aspects
Protein Transport - radiation effects
Receptors
Recoverin
Retina
Retina - cytology
Retina - growth & development
Retina - metabolism
Retina - radiation effects
Retinal ganglion cells
RNA, Small Interfering - metabolism
Rods
Staining and Labeling
Studies
Thyroid gland
Transcription
Transcription (Genetics)
Transcriptional Activation - genetics
Transcriptional Activation - radiation effects
Veterinary Science
title Nuclear receptor Rev-erb alpha (Nr1d1) functions in concert with Nr2e3 to regulate transcriptional networks in the retina
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