ArticleGene therapy2010
Quantitative fine-tuning of photoreceptor cis-regulatory elements through affinity modulation of transcription factor binding sites.
Article in Gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Aberrant homeodomain-DNA cooperative dimerization underlies distinct developmental defects in two dominantGenome research · 2025Article
- Active learning of enhancers and silencers in the developing neural retina.Cell systems · 2025Article
- Pathogenic variants inGenome research · 2024Article
- Aberrant homeodomain-DNA cooperative dimerization underlies distinct developmental defects in two dominantbioRxiv : the preprint server for biology · 2024Article
- Pathogenic variants in Crx have distinct cis-regulatory effects on enhancers and silencers in photoreceptors.bioRxiv : the preprint server for biology · 2023Article
- Missense mutations in CRX homeodomain cause dominant retinopathies through two distinct mechanisms.eLife · 2023Article
- Developmental genome-wide occupancy analysis of bZIP transcription factor NRL uncovers the role of c-Jun in early differentiation of rod photoreceptors in the mammalian retina.Human molecular genetics · 2022Article
- Mutations inScience advances · 2022Article
- An enhancer located in a Pde6c intron drives transient expression in the cone photoreceptors of developing mouse and human retinas.Developmental biology · 2022Article
- A Modified Arrestin1 Increases Lactate Production in the Retina and Slows Retinal Degeneration.Human gene therapy · 2022Article
- Interaction of human CRX and NRL in live HEK293T cells measured using fluorescence resonance energy transfer (FRET).Scientific reports · 2022Article
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- A massively parallel reporter assay reveals context-dependent activity of homeodomain binding sites in vivo.Genome research · 2018Article
- In silico modeling of epigenetic-induced changes in photoreceptor cis-regulatory elements.Molecular vision · 2018Article
- The X-linked juvenile retinoschisis protein retinoschisin is a novel regulator of mitogen-activated protein kinase signalling and apoptosis in the retina.Journal of cellular and molecular medicine · 2017Article
- Cell Type-Specific Epigenomic Analysis Reveals a Uniquely Closed Chromatin Architecture in Mouse Rod Photoreceptors.Scientific reports · 2017Article
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- A Simple Grammar Defines Activating and Repressing cis-Regulatory Elements in Photoreceptors.Cell reports · 2016Article
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Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Given the remarkable recent progress in gene therapy-based treatments for retinal disease, there is an urgent need for the development of new approaches to quantitative design and analysis of photoreceptor-specific promoters. In this study, we determined the relative binding affinity of all single-nucleotide variants of the consensus binding site of the mammalian photoreceptor transcription factor, Crx. We then showed that it is possible to use these data to accurately predict the relative binding affinity of Crx for all possible 8 bp sequences. By rationally adjusting the binding affinity of three Crx sites, we were able to fine-tune the expression of the rod-specific Rhodopsin promoter over a 225-fold range in living retinas. In addition, we showed that it is possible to fine-tune the activity of the rod-specific Gnat1 promoter over ∼275-fold range by modulating the affinity of a single Crx-binding site. We found that the action of individual binding sites depends on the precise promoter context of the site and that increasing binding affinity does not always equate with increased promoter output. Despite these caveats, this tuning approach permits quantitative engineering of photoreceptor-specific cis-regulatory elements, which can be used as drivers in gene therapy vectors for the treatment of blindness.
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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.