ArticleMolecular and cellular biology2011
Hypoxia-induced epigenetic regulation and silencing of the BRCA1 promoter.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 134 citations in OpenAlex.
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Hypoxic adaptation theory of cancer.Frontiers in cell and developmental biology · 2026Article
- Hypoxia Induces Immunosuppression by Silencing STING in Cancer.Cancer research · 2025Article
- Hypoxia Imaging as a Radiomics Signature in Tumors Using NovelbioRxiv : the preprint server for biology · 2025Article
- PRMT5 regulates alternative splicing of TCF3 under hypoxia to promote EMT and invasion in breast cancer.PLoS biology · 2025Article
- Review
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- Hypoxia-induced ATF3 escalates breast cancer invasion by increasing collagen deposition via P4HA1.Cell death & disease · 2025Article
- Targeting synthetic lethality: an effective therapeutic approach in ovarian and endometrial cancers.Therapeutic advances in medical oncology · 2025Review
- Hypoxia alters the response of ovarian cancer cells to the mitomycin C drug.Frontiers in cell and developmental biology · 2025Article
- Hypoxia-induced epigenetic regulation of breast cancer progression and the tumour microenvironment.Frontiers in cell and developmental biology · 2024Review
- Vitamin C: From nutrition to oxygen sensing and epigenetics.Redox biology · 2023Article
- Targeted therapy and immunotherapy: Diamonds in the rough in the treatment of epithelial ovarian cancer.Frontiers in pharmacology · 2023Review
- Article
- The Breast Cancer Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis.Antioxidants (Basel, Switzerland) · 2022Review
- Development of a sensitive, quantitative assay with broad subtype specificity for detection of total HIV-1 nucleic acids in plasma and PBMC.Scientific reports · 2022Article
- Connections between metabolism and epigenetic modifications in cancer.Medical review (2021) · 2021Review
- Understanding and overcoming resistance to PARP inhibitors in cancer therapy.Nature reviews. Clinical oncology · 2021Review
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- The roles of inducible chromatin and transcriptional memory in cellular defense system responses to redox-active pollutants.Free radical biology & medicine · 2021Review
16 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Disruption of the BRCA1 tumor suppressor can be caused not only by inherited mutations in familial cancers but also by BRCA1 gene silencing in sporadic cancers. Hypoxia, a key feature of the tumor microenvironment, has been shown to downregulate BRCA1 at the transcriptional level via repressive E2F4/p130 complexes. Here we showed that hypoxia also drives epigenetic modification of the BRCA1 promoter, with decreased H3K4 methylation as a key repressive modification produced by the lysine-specific histone demethylase LSD1. We also observed increased H3K9 methylation coupled with decreased H3K9 acetylation. Similar modifications were seen in the RAD51 promoter, which is also downregulated by hypoxia, whereas exactly opposite changes were seen in the promoter of the hypoxia-inducible gene VEGF. In cells containing the BRCA1 promoter driving a selectable HPRT gene, long-term silencing of the promoter was observed following exposure to hypoxic stress. Clones with silenced BRCA1 promoters were detected at frequencies of 2% or more following hypoxia, but at less than 6 × 10(-5) without hypoxia. The silenced clones showed decreased H3K4 methylation and decreased H3K9 acetylation in the BRCA1 promoters, consistent with the acute effects of hypoxic stress. Hypoxia-induced BRCA1 promoter silencing persisted in subsequent normoxic conditions but could be reversed by treatment with a histone deacetylase (HDAC) inhibitor but not with a DNA methylation inhibitor. Interestingly, treatment of cells with inhibitors of poly(ADP-ribose) polymerase (PARP) can cause short-term repression of BRCA1 expression, but such treatment does not produce H3K4 or H3K9 histone modification or BRCA1 promoter silencing. These results suggest that hypoxia is a driving force for long-term silencing of BRCA1, thereby promoting genome instability and tumor progression.
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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.