ArticleCell death & disease2018
DZNep inhibits H3K27me3 deposition and delays retinal degeneration in the rd1 mice.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- AHCY: A metabolic gatekeeper at the interface of methylation, redox balance, and cellular stress response.The Journal of biological chemistry · 2026Review
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- Inhibiting miR-155-5p promotes proliferation of human submandibular gland epithelial cells in primary Sjogren's syndrome by negatively regulating the PI3K/AKT signaling pathwayNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Exploring Histone Modifications in Inherited Retinal Disorders.Advances in experimental medicine and biology · 2025Review
- Epigenetic Switches in Retinal Homeostasis and Target for Drug Development.International journal of molecular sciences · 2024Review
- Exploring Epigenetic Modifications as Potential Biomarkers and Therapeutic Targets in Glaucoma.International journal of molecular sciences · 2024Review
- Hyperglycemia-independent neonatal streptozotocin-induced retinopathy (NSIR) in rats.Frontiers in pharmacology · 2024Article
- The roles of EZH2 in cancer and its inhibitors.Medical oncology (Northwood, London, England) · 2023Review
- The role of epigenetic changes in the pathology and treatment of inherited retinal diseases.Frontiers in cell and developmental biology · 2023Review
- The role of epigenetic methylation/demethylation in the regulation of retinal photoreceptors.Frontiers in cell and developmental biology · 2023Review
- SETDB1 acts as a topological accessory to Cohesin via an H3K9me3-independent, genomic shunt for regulating cell fates.Nucleic acids research · 2022Article
- Increased H3K27 trimethylation contributes to cone survival in a mouse model of cone dystrophy.Cellular and molecular life sciences : CMLS · 2022Article
- Review
- Neuroinflammation in retinitis pigmentosa: Therapies targeting the innate immune system.Frontiers in immunology · 2022Review
- Enhancer of Zeste Homolog 2 (EZH2) Contributes to Rod Photoreceptor Death Process in Several Forms of Retinal Degeneration and Its Activity Can Serve as a Biomarker for Therapy Efficacy.International journal of molecular sciences · 2021Article
- 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
- Epigenetic regulation of retinal development.Epigenetics & chromatin · 2021Review
- Combination of AZD3463 and DZNep Prevents Bone Metastasis of Breast Cancer by Suppressing Akt Signaling.Frontiers in pharmacology · 2021Article
- AnFrontiers in neuroscience · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases causing progressive loss of photoreceptors. Numerous gene mutations are identified to be related with RP, but epigenetic modifications may also be involved in the pathogenesis. Previous studies suggested that both DNA methylation and histone acetylation regulate photoreceptor cell death in RP mouse models. However, the role of histone methylation in RP has never been investigated. In this study, we found that trimethylation of several lysine sites of histone H3, including lysine 27 (H3K27me3), increased in the retinas of rd1 mice. Histone methylation inhibitor DZNep significantly reduced the calpain activity, delayed the photoreceptor loss, and improved ERG response of rd1 retina. RNA-sequencing indicated that DZNep synergistically acts on several molecular pathways that regulate photoreceptor survival in rd1 retina, including PI3K-Akt and photoreceptor differentiation pathways, revealing the therapeutic potential of DZNep for RP treatment. PI3K-Akt pathway and H3K27me3 form a feedback loop in rd1 retina, thus PI3K inhibitor LY294002 reduces phosphorylation of Ezh2 at serine 21 and enhances H3K27me3 deposition, and inhibiting H3K27me3 by DZNep can activate PI3K-Akt pathway by de-repressing gene expression of PI3K subunits Pik3r1 and Pik3r3. These findings suggest that histone methylation, especially H3K27me3 deposition is a novel mechanism and therapeutic target for retinal degenerative diseases, similar to H3K27me3-mediated ataxia-telangiectasia in Atm
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