ArticleeLife2017
Loss of Dnmt3a and Dnmt3b does not affect epidermal homeostasis but promotes squamous transformation through PPAR-γ.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- The extracellular matrix: structure, composition, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- Epigenetic Regulation of Sebaceous and Meibomian Glands: From Development to Disease.Biomedicines · 2026Review
- Understanding epigenetic regulation in the endometrium - lessons from mouse models with implantation defects.Epigenomics · 2025Review
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
- Epigenetics in Skin Homeostasis and Ageing.Epigenomes · 2025Review
- Bridging tissue repair and epithelial carcinogenesis: epigenetic memory and field cancerization.Cell death and differentiation · 2025Review
- Stem cell activity-coupled suppression of endogenous retrovirus governs adult tissue regeneration.Cell · 2024Article
- Review
- Dual function of activated PPARγ by ligands on tumor growth and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Direct Lineage Reprogramming for Induced Keratinocyte Stem Cells: A Potential Approach for Skin Repair.Stem cells translational medicine · 2023Review
- Melanoma in a patient with DNMT3A overgrowth syndrome.Cold Spring Harbor molecular case studies · 2023Article
- Initiation of wound healing is regulated by the convergence of mechanical and epigenetic cues.PLoS biology · 2022Article
- Comparative transcriptomics reveals circadian and pluripotency networks as two pillars of longevity regulation.Cell metabolism · 2022Article
- Loss of TET2 Tips the Scales Toward Tumorigenesis.The Journal of investigative dermatology · 2022Article
- Toward Elucidating Epigenetic and Metabolic Regulation of Stem Cell Lineage Plasticity in Skin Aging.Frontiers in cell and developmental biology · 2022Review
- Epigenetic and metabolic interplay in cutaneous squamous cell carcinoma.Experimental dermatology · 2021Article
- Terminal keratinocyte differentiation in vitro is associated with a stable DNA methylome.Experimental dermatology · 2021Article
- Epigenetic and metabolic regulation of epidermal homeostasis.Experimental dermatology · 2021Review
- Skin epigenetics.Experimental dermatology · 2021Article
- Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The DNA methyltransferase Dnmt3a suppresses tumorigenesis in models of leukemia and lung cancer. Conversely, deregulation of Dnmt3b is thought to generally promote tumorigenesis. However, the role of Dnmt3a and Dnmt3b in many types of cancer remains undefined. Here, we show that Dnmt3a and Dnmt3b are dispensable for homeostasis of the murine epidermis. However, loss of Dnmt3a-but not Dnmt3b-increases the number of carcinogen-induced squamous tumors, without affecting tumor progression. Only upon combined deletion of Dnmt3a and Dnmt3b, squamous carcinomas become more aggressive and metastatic. Mechanistically, Dnmt3a promotes the expression of epidermal differentiation genes by interacting with their enhancers and inhibits the expression of lipid metabolism genes, including PPAR-γ, by directly methylating their promoters. Importantly, inhibition of PPAR-γ partially prevents the increase in tumorigenesis upon deletion of Dnmt3a. Altogether, we demonstrate that Dnmt3a and Dnmt3b protect the epidermis from tumorigenesis and that squamous carcinomas are sensitive to inhibition of PPAR-γ.
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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.