ArticleHuman molecular genetics2009
BEST1 expression in the retinal pigment epithelium is modulated by OTX family members.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
- NAD+ modulates mitochondrial vulnerability in MERTK-associated models of retinitis pigmentosa.Nature communications · 2026Article
- Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate causal variants in macular degeneration.Cell reports · 2026Article
- From BEST1 mutations to retinal regeneration: integrating stem cell-derived RPE models and gene correction strategies.Frontiers in cell and developmental biology · 2026Review
- CRX is an intrinsic suppressor of epithelial‒mesenchymal transition in retinal pigment epithelial cells: a promising therapeutic avenue for subretinal fibrosis.Cell death & disease · 2025Article
- Cone Rod Homeobox (Ophthalmic genetics · 2025Review
- A biometric survey of known and prospective murine models of posterior microphthalmia-nanophthalmia.Experimental eye research · 2025Article
- Functional genomics in age-related macular degeneration: From genetic associations to understanding disease mechanisms.Experimental eye research · 2025Review
- Micropulse transscleral cyclophotocoagulation in the treatment of autosomal recessive bestrophinopathy combined with angle closure glaucoma: a case report.Frontiers in medicine · 2025Article
- Review
- Exploring ocular fibulin-3 (EFEMP1): Anatomical, age-related, and species perspectives.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Clinical and genetic features in autosomal recessive bestrophinopathy in Chinese cohort.BMC ophthalmology · 2024Article
- Txnip deletions and missense alleles prolong the survival of cones in a retinitis pigmentosa mouse model.eLife · 2024Article
- Txnip deletions and missense alleles prolong the survival of cones in a retinitis pigmentosa mouse model.bioRxiv : the preprint server for biology · 2024Article
- Label-free enrichment of human pluripotent stem cell-derived early retinal progenitor cells for cell-based regenerative therapies.Stem cell reports · 2024Article
- Best Disease: Global Mutations Review, Genotype-Phenotype Correlation, and Prevalence Analysis in the Israeli Population.Investigative ophthalmology & visual science · 2024Article
- SIRT6 overexpression in the nucleus protects mouse retinal pigment epithelium from oxidative stress.Life science alliance · 2023Article
- Visual function restoration in a mouse model of Leber congenital amaurosis via therapeutic base editing.Molecular therapy. Nucleic acids · 2023Article
- The LHX2-OTX2 transcriptional regulatory module controls retinal pigmented epithelium differentiation and underlies genetic risk for age-related macular degeneration.PLoS biology · 2023Article
- Impaired Bestrophin Channel Activity in an iPSC-RPE Model of Best Vitelliform Macular Dystrophy (BVMD) from an Early Onset Patient Carrying the P77S Dominant Mutation.International journal of molecular sciences · 2022Article
- Inducing human retinal pigment epithelium-like cells from somatic tissue.Stem cell reports · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
A number of genes preferentially expressed in the retinal pigment epithelium (RPE) are associated with retinal degenerative disease. One of these, BEST1, encodes bestrophin-1, a protein that when mutated causes Best macular dystrophy. As a model for RPE gene regulation, we have been studying the mechanisms that control BEST1 expression, and recently demonstrated that members of the MITF-TFE family modulate BEST1 transcription. The human BEST1 upstream region from -154 to +38 bp is sufficient to direct expression in the RPE, and positive-regulatory elements exist between -154 and -104 bp. Here, we show that the -154 to -104 bp region is necessary for RPE expression in transgenic mice and contains a predicted OTX-binding site (Site 1). Since another non-canonical OTX site (Site 2) is located nearby, we tested the function of these sites using BEST1 promoter/luciferase constructs by in vivo electroporation and found that mutation of both sites reduces promoter activity. Three OTX family proteins - OTX1, OTX2 and CRX - bound to both Sites 1 and 2 in vitro, and all of them increased BEST1 promoter activity. Surprisingly, we found that human and bovine RPE expressed not only OTX2 but also CRX, the CRX genomic region in bovine RPE was hypersensitive to DNase I, consistent with active transcription, and that both OTX2 and CRX bound to the BEST1 proximal promoter in vivo. These results demonstrate for the first time CRX expression in the RPE, and suggest that OTX2 and CRX may act as positive modulators of the BEST1 promoter in the RPE.
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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.