Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors

Cheng, H.

doi:10.1093/hmg/ddh173

Cited by 268Retinal Development and DisordersNuclear Receptors and SignalingRetinoids in leukemia and cellular processes

Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors

Cheng, H.·2004·Human Molecular Genetics

DOI 10.1093/hmg/ddh173

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Abstract

NR2E3, a photoreceptor-specific orphan nuclear receptor, is believed to play a pivotal role in the differentiation of photoreceptors. Mutations in the human NR2E3 gene and its mouse ortholog are associated with enhanced S-cones and retinal degeneration. In order to gain insights into the NR2E3 function, we performed temporal and spatial expression analysis, yeast two-hybrid screening, promoter activity assays and co-immunoprecipitation studies. The Nr2e3 expression was localized preferentially to the rod, and not to the cone, photoreceptor nuclei in rodent retina. The yeast two-hybrid screening of a retinal cDNA library, using NR2E3 as the bait, identified another orphan nuclear receptor NR1D1 (Rev-erbalpha). The interaction of NR2E3 with NR1D1 was confirmed by glutathione S-transferase pulldown and co-immunoprecipitation experiments. In transient transfection studies using HEK 293 cells, both NR2E3 and NR1D1 activated the promoters of rod phototransduction genes synergistically with neural retina leucine zipper (NRL) and cone-rod homeobox (CRX). All four proteins, NR2E3, NR1D1, NRL and CRX, could be co-immunoprecipitated from the bovine retinal nuclear extract, suggesting their existence in a multi-protein transcriptional regulatory complex in vivo. Our results demonstrate that NR2E3 is involved in regulating the expression of rod photoreceptor-specific genes and support its proposed role in transcriptional regulatory network(s) during rod differentiation.

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Nr2e3 is part of the cellular and nuclear receptor family for steroid hormones and is involved in cone cell proliferation, maintenance of photoreceptor topography and intercellular interactions, and expression of rod photoreceptor cell-specific genes.
“Nr2e3 is part of the cellular and nuclear receptor family for steroid hormones and is involved in cone cell proliferation, maintenance of photoreceptor topography and intercellular interactions, and expression of rod photoreceptor cell-specific genes”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Cheng et al., 2004

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Authors: Cheng, H.
Affiliations: University of Michigan (US)
Corresponding author: Cheng, H.
ORCID: Cheng, H.
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 2004-08-01
Volume: 13
Issue: 15
Pages: 1563-1575
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/ddh173
OpenAlex: W2136899592
Cited by: 268
References: 61
Citations by year: 2026: 9 · 2025: 14 · 2024: 17 · 2023: 16 · 2022: 14 · 2021: 10 · 2020: 13 · 2019: 6 · 2018: 8 · 2017: 11 · 2016: 11 · 2015: 7 · 2014: 15 · 2013: 9 · 2012: 14
FWCI: 5.22
Type: journal article
Language: en
Open access: closed
Locations: Human Molecular Genetics (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: National Institutes of Health (5r24ey014803-05)
National Eye Institute (EY11115, EY 07003, R01EY011115, EY014803)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
Keywords: NR2E3, orphan nuclear receptor, rod photoreceptors, transcriptional activation, NR1D1, photoreceptor differentiation, NRL, CRX, phototransduction genes, transcriptional regulatory complexes, retinal degeneration, S-cones
MeSH terms: Animals, DNA-Binding Proteins, Eye Proteins, Glutathione Transferase, Humans, Precipitin Tests, Promoter Regions, Genetic, Rhodopsin, Transcription Factors, Transcription, Genetic, Transducin, Trans-Activators, Retinal Rod Photoreceptor Cells, Receptors, Cytoplasmic and Nuclear, Homeodomain Proteins, Two-Hybrid System Techniques, Heterotrimeric GTP-Binding Proteins, GTP-Binding Protein alpha Subunits, Basic-Leucine Zipper Transcription Factors, Mice, Nuclear Receptor Subfamily 1, Group D, Member 1, Orphan Nuclear Receptors

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Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors

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