ArticleThe Journal of biological chemistry2014
Transcription factor SOX9 plays a key role in the regulation of visual cycle gene expression in the retinal pigment epithelium.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- Article
- Programming human cell type-specific gene expression via an atlas of AI-designed enhancers.bioRxiv : the preprint server for biology · 2025Article
- Regulation of RPE65 expression in human retinal pigment epithelium cells.Scientific reports · 2025Article
- Article
- Increased water temperature contributes to a chondrogenesis response in the eyes of spotted wolffish.Scientific reports · 2024Article
- Article
- The Effects of the Coating and Aging of Biodegradable Polylactic Acid Membranes on In Vitro Primary Human Retinal Pigment Epithelium Cells.Biomedicines · 2024Article
- DHA Shortage Causes the Early Degeneration of Photoreceptors and RPE in Mice With Peroxisomal β-Oxidation Deficiency.Investigative ophthalmology & visual science · 2023Article
- Contralateral Astrocyte Response to Acute Optic Nerve Damage Is Mitigated by PANX1 Channel Activity.International journal of molecular sciences · 2023Article
- Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity.iScience · 2023Article
- SWI/SNF complexes are required for retinal pigmented epithelium differentiation and for the inhibition of cell proliferation and neural differentiation programs.Development (Cambridge, England) · 2023Article
- SIRT6 overexpression in the nucleus protects mouse retinal pigment epithelium from oxidative stress.Life science alliance · 2023Article
- Article
- The LHX2-OTX2 transcriptional regulatory module controls retinal pigmented epithelium differentiation and underlies genetic risk for age-related macular degeneration.PLoS biology · 2023Article
- SOX9 in organogenesis: shared and unique transcriptional functions.Cellular and molecular life sciences : CMLS · 2022Review
- Direct conversion of human umbilical cord mesenchymal stem cells into retinal pigment epithelial cells for treatment of retinal degeneration.Cell death & disease · 2022Article
- Arap1 loss causes retinal pigment epithelium phagocytic dysfunction and subsequent photoreceptor death.Disease models & mechanisms · 2022Article
- Review
- A Stage-Specific OTX2 Regulatory Network and Maturation-Associated Gene Programs Are Inherent Barriers to RPE Neural Competency.Frontiers in cell and developmental biology · 2022Article
- SOX9 in Keratinocytes Regulates Claudin 2 Transcription during Skin Aging.Contrast media & molecular imaging · 2022Article
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
The retinal pigment epithelium (RPE) performs specialized functions to support retinal photoreceptors, including regeneration of the visual chromophore. Enzymes and carrier proteins in the visual cycle function sequentially to regenerate and continuously supply 11-cis-retinal to retinal photoreceptor cells. However, it is unknown how the expression of the visual cycle genes is coordinated at the transcriptional level. Here, we show that the proximal upstream regions of six visual cycle genes contain chromatin-accessible sex-determining region Y box (SOX) binding sites, that SOX9 and LIM homeobox 2 (LHX2) are coexpressed in the nuclei of mature RPE cells, and that SOX9 acts synergistically with orthodenticle homeobox 2 (OTX2) to activate the RPE65 and retinaldehyde binding protein 1 (RLBP1) promoters and acts synergistically with LHX2 to activate the retinal G protein-coupled receptor (RGR) promoter. ChIP reveals that SOX9 and OTX2 bind to the promoter regions of RPE65, RLBP1, and RGR and that LHX2 binds to those of RPE65 and RGR in bovine RPE. ChIP with human fetal RPE cells shows that SOX9 and OTX2 also bind to the human RPE65, RLBP1, and RGR promoters. Conditional inactivation of Sox9 in mouse RPE results in reduced expression of several visual cycle genes, most dramatically Rpe65 and Rgr. Furthermore, bioinformatic analysis predicts that multiple common microRNAs (miRNAs) regulate visual cycle genes, and cotransfection of miRNA mimics with luciferase reporter constructs validated some of the predicted miRNAs. These results implicate SOX9 as a key regulator of visual cycle genes, reveal for the first time the functional role of LHX2 in the RPE, and suggest the possible regulation of visual cycle genes by common miRNAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.