ArticleEpigenetics & chromatin2016
Hypoxia increases genome-wide bivalent epigenetic marking by specific gain of H3K27me3.
Article in Epigenetics & chromatin, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 86 citations in OpenAlex.
- Biomolecular Condensates Integrate Transcriptional and Epigenetic Responses to Hypoxia.International journal of molecular sciences · 2026Review
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
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- Co-occurrence of transcriptionally distinct persister cell states underpins neoadjuvant therapy resistance in triple‑negative breast cancer.Genome medicine · 2026Article
- Comparative analyses of ChIP-seq, CUT&RUN and CUT&Tag for Polycomb chromatin profiling.BMB reports · 2026Article
- Hypoxic regulation of chromatin and gene transcription.Communications biology · 2026Article
- Hypoxic adaptation theory of cancer.Frontiers in cell and developmental biology · 2026Article
- Circadian clock and cancer.Military Medical Research · 2026Review
- Epigenetic alterations facilitate transcriptional and translational programs in hypoxia.Nature cell biology · 2025Article
- HypoxamiRs: the hidden architects of tissue adaptation in hypoxia.Cell death & disease · 2025Review
- EZH2 variants derived from cryptic splice sites govern distinct epigenetic patterns during embryonic development.Nucleic acids research · 2025Article
- Fusobacterium nucleatum infection modulates the transcriptome and epigenome of HCT116 colorectal cancer cells in an oxygen-dependent manner.Communications biology · 2024Article
- The involvement of RNA N6-methyladenosine and histone methylation modification in decidualization and endometriosis-associated infertility.Clinical and translational medicine · 2024Article
- Oxygen-regulated post-translation modifications as master signalling pathway in cells.EMBO reports · 2023Review
- Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype.Science advances · 2023Review
- Variation in histone configurations correlates with gene expression across nine inbred strains of mice.Genome research · 2023Article
- Metabolic reprogramming and epigenetic modifications on the path to cancer.Protein & cell · 2022Review
- Tumor microenvironmental signals reshape chromatin landscapes to limit the functional potential of exhausted T cells.Science immunology · 2022Article
- Gene regulation by histone-modifying enzymes under hypoxic conditions: a focus on histone methylation and acetylation.Experimental & molecular medicine · 2022Review
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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
backgroundTrimethylation at histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) controls gene activity during development and differentiation. Whether H3K4me3 and H3K27me3 changes dynamically in response to altered microenvironmental conditions, including low-oxygen conditions commonly present in solid tumors, is relatively unknown. Demethylation of H3K4me3 and H3K27me3 is mediated by oxygen and 2-oxoglutarate dioxygenases enzymes, suggesting that oxygen deprivation (hypoxia) may influence histone trimethylation. Using the MCF7 breast epithelial adenocarcinoma cell model, we have determined the relationship between epigenomic and transcriptomic reprogramming as a function of fluctuating oxygen tension.
resultsWe find that in MCF7, H3K4me3 and H3K27me3 marks rapidly increase at specific locations throughout the genome and are largely reversed upon reoxygenation. Whereas dynamic changes are relatively highest for H3K27me3 marking under hypoxic conditions, H3K4me3 occupation is identified as the defining epigenetic marker of transcriptional control. In agreement with the global increase of H3K27 trimethylation, we provide direct evidence that the histone H3K27me3 demethylase KDM6B/JMJD3 is inactivated by limited oxygen. In situ immunohistochemical analysis confirms a marked rise of histone trimethylation in hypoxic tumor areas. Acquisition of H3K27me3 at H3K4me3-marked loci results in a striking increase in "bivalent" epigenetic marking. Hypoxia-induced bivalency substantially overlaps with embryonal stem cell-associated genic bivalency and is retained at numerous loci upon reoxygenation. Transcriptional activity is selectively and progressively dampened at bivalently marked loci upon repeated exposure to hypoxia, indicating that this subset of genes uniquely maintains the potential for epigenetic regulation by KDM activity.
conclusionsThese data suggest that dynamic regulation of the epigenetic state within the tumor environment may have important consequences for tumor plasticity and biology.
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