ArticleCell death & disease2014
DNA methylation and differential gene regulation in photoreceptor cell death.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- DNA hypermethylation-mediated downregulation of antioxidant genes contributes to the early onset of cataracts in highly myopic eyes.Redox biology · 2018Trial
- Single-cell analysis reveals impaired Müller glia-mediated intercellular communication and photoreceptor pathology in USH1C retinal organoids.Cellular and molecular life sciences : CMLS · 2026Article
- DNA Methylation Dynamics in a Mouse Model of Retinitis Pigmentosa.The American journal of pathology · 2025Article
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Epigenome-metabolism nexus in the retina: implications for aging and disease.Trends in genetics : TIG · 2024Review
- Epigenetic Switches in Retinal Homeostasis and Target for Drug Development.International journal of molecular sciences · 2024Review
- Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease.Frontiers in cellular neuroscience · 2024Review
- Suppressing DNMT3a Alleviates the Intrinsic Epigenetic Barrier for Optic Nerve Regeneration and Restores Vision in Adult Mice.bioRxiv : the preprint server for biology · 2023Article
- Review
- Rapid detection of cancer DNA in human blood using cysteamine-capped AuNPs and a machine learning-enabled smartphone.RSC advances · 2023Article
- The role of epigenetic methylation/demethylation in the regulation of retinal photoreceptors.Frontiers in cell and developmental biology · 2023Review
- The role of epigenetic changes in the pathology and treatment of inherited retinal diseases.Frontiers in cell and developmental biology · 2023Review
- Review
- Regulation of Developmental Cell Death in the Animal Kingdom: A Critical Analysis of Epigenetic versus Genetic Factors.International journal of molecular sciences · 2022Review
- Decitabine improves MMS-induced retinal photoreceptor cell damage by targeting DNMT3A and DNMT3B.Frontiers in molecular neuroscience · 2022Article
- Neuroinflammation in retinitis pigmentosa: Therapies targeting the innate immune system.Frontiers in immunology · 2022Review
- Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke.International journal of molecular sciences · 2021Article
- Epigenetic regulation in Huntington's disease.Neurochemistry international · 2021Review
- Inhibition of Epigenetic Modifiers LSD1 and HDAC1 Blocks Rod Photoreceptor Death in Mouse Models of Retinitis Pigmentosa.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- The methylation status of the embryonic limb skeletal progenitors determines their cell fate in chicken.Communications biology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinitis pigmentosa (RP) defines a group of inherited degenerative retinal diseases causing progressive loss of photoreceptors. To this day, RP is still untreatable and rational treatment development will require a thorough understanding of the underlying cell death mechanisms. Methylation of the DNA base cytosine by DNA methyltransferases (DNMTs) is an important epigenetic factor regulating gene expression, cell differentiation, cell death, and survival. Previous studies suggested an involvement of epigenetic mechanisms in RP, and in this study, increased cytosine methylation was detected in dying photoreceptors in the rd1, rd2, P23H, and S334ter rodent models for RP. Ultrastructural analysis of photoreceptor nuclear morphology in the rd1 mouse model for RP revealed a severely altered chromatin structure during retinal degeneration that coincided with an increased expression of the DNMT isozyme DNMT3a. To identify disease-specific differentially methylated DNA regions (DMRs) on a genomic level, we immunoprecipitated methylated DNA fragments and subsequently analyzed them with a targeted microarray. Genome-wide comparison of DMRs between rd1 and wild-type retina revealed hypermethylation of genes involved in cell death and survival as well as cell morphology and nervous system development. When correlating DMRs with gene expression data, we found that hypermethylation occurred alongside transcriptional repression. Consistently, motif analysis showed that binding sites of several important transcription factors for retinal physiology were hypermethylated in the mutant model, which also correlated with transcriptional silencing of their respective target genes. Finally, inhibition of DNMTs in rd1 organotypic retinal explants using decitabine resulted in a substantial reduction of photoreceptor cell death, suggesting inhibition of DNA methylation as a potential novel treatment in RP.
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