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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0017494</identifier><identifier>PMID: 21408158</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2011-03, Vol.6 (3), p.e17494-e17494</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Mollema et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Mollema et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c625t-9ded55b21ff93e915929c9e7b4e1c1ff0bd32e9d086bf2bb589e6a4295e841773</citedby><cites>FETCH-LOGICAL-c625t-9ded55b21ff93e915929c9e7b4e1c1ff0bd32e9d086bf2bb589e6a4295e841773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050883/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050883/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21408158$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Nollen, Ellen</contributor><creatorcontrib>Mollema, Nissa J</creatorcontrib><creatorcontrib>Yuan, Yang</creatorcontrib><creatorcontrib>Jelcick, Austin S</creatorcontrib><creatorcontrib>Sachs, Andrew J</creatorcontrib><creatorcontrib>von Alpen, Désirée</creatorcontrib><creatorcontrib>Schorderet, Daniel</creatorcontrib><creatorcontrib>Escher, Pascal</creatorcontrib><creatorcontrib>Haider, Neena B</creatorcontrib><title>Nuclear receptor Rev-erb alpha (Nr1d1) functions in concert with Nr2e3 to regulate transcriptional networks in the retina</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Aging - metabolism</subject><subject>Aging - radiation effects</subject><subject>Animals</subject><subject>Biology</subject><subject>Cell Count</subject><subject>Circadian rhythms</subject><subject>Cofactors</subject><subject>Concerts</subject><subject>Cones</subject><subject>Electroretinograms</subject><subject>Enhancer Elements, Genetic - genetics</subject><subject>Gene expression</subject><subject>Gene Regulatory Networks - genetics</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic research</subject><subject>Genetics</subject><subject>Injections</subject><subject>Ligands</subject><subject>Light</subject><subject>Light Signal Transduction - genetics</subject><subject>Light Signal Transduction - radiation effects</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Musculoskeletal system</subject><subject>Mutation</subject><subject>Networks</subject><subject>Nuclear Receptor Subfamily 1, Group D, Member 1 - 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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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