ArticleNucleic acids research2020
Targeted DNA oxidation by LSD1-SMAD2/3 primes TGF-β1/ EMT genes for activation or repression.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Hydrogen peroxide sensing and signaling in physiology and disease: implications for therapy.Signal transduction and targeted therapy · 2026Review
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- Strand-specific quantification of 8-oxo-dG and apurinic sites via Ligation-Dependent Probe Amplification (LPA).Redox biology · 2025Article
- NOX-NOS crosstalk in the liver-brain axis: Novel insights for redox regulation and neurodegenerative diseases.Redox biology · 2025Review
- p53-inducible lncRNA LOC644656 causes genotoxic stress-induced stem cell maldifferentiation and cancer chemoresistance.Nature communications · 2025Article
- Redox-Driven Epigenetic Modifications in Sperm: Unraveling Paternal Influences on Embryo Development and Transgenerational Health.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- The Role of Epithelial-Mesenchymal Transition in Osteosarcoma Progression: From Biology to Therapy.Diagnostics (Basel, Switzerland) · 2025Review
- Review
- Research on Predicting the Occurrence of Hepatocellular Carcinoma Based on Notch Signal-Related Genes Using Machine Learning Algorithms.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023Article
- Inflammation and DNA damage: cause, effect or both.Nature reviews. Rheumatology · 2023Review
- Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage.Nature communications · 2023Article
- 8-Oxoguanine targeted by 8-oxoguanine DNA glycosylase 1 (OGG1) is central to fibrogenic gene activation upon lung injury.Nucleic acids research · 2023Article
- The Intertwined Role of 8-oxodG and G4 in Transcription Regulation.International journal of molecular sciences · 2023Review
- Substrate-specific binding of 8-oxoguanine DNA glycosylase 1 (OGG1) reprograms mucosal adaptations to chronic airway injury.Frontiers in immunology · 2023Review
- Arginine methylation in the epithelial-to-mesenchymal transition.The FEBS journal · 2022Review
- 8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification.Experimental & molecular medicine · 2022Review
- 8-oxodG accumulation within super-enhancers marks fragile CTCF-mediated chromatin loops.Nucleic acids research · 2022Article
- LSD1-S112A exacerbates the pathogenesis of CSE/LPS-induced chronic obstructive pulmonary disease in mice.BMB reports · 2021Article
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epithelial-to-mesenchymal transition (EMT) is a complex transcriptional program induced by transforming growth factor β1 (TGF-β1). Histone lysine-specific demethylase 1 (LSD1) has been recognized as a key mediator of EMT in cancer cells, but the precise mechanism that underlies the activation and repression of EMT genes still remains elusive. Here, we characterized the early events induced by TGF-β1 during EMT initiation and establishment. TGF-β1 triggered, 30-90 min post-treatment, a nuclear oxidative wave throughout the genome, documented by confocal microscopy and mass spectrometry, mediated by LSD1. LSD1 was recruited with phosphorylated SMAD2/3 to the promoters of prototypic genes activated and repressed by TGF-β1. After 90 min, phospho-SMAD2/3 downregulation reduced the complex and LSD1 was then recruited with the newly synthesized SNAI1 and repressors, NCoR1 and HDAC3, to the promoters of TGF-β1-repressed genes such as the Wnt soluble inhibitor factor 1 gene (WIF1), a change that induced a late oxidative burst. However, TGF-β1 early (90 min) repression of transcription also required synchronous signaling by reactive oxygen species and the stress-activated kinase c-Jun N-terminal kinase. These data elucidate the early events elicited by TGF-β1 and the priming role of DNA oxidation that marks TGF-β1-induced and -repressed genes involved in the EMT.
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