Trimethylation of histone H3 at lysine 4 (H3K4me3) is a marker of active promoters. Broad H3K4me3 promoter domains have been associated with cell type identity, but H3K4me3 dynamics upon cellular stress have not been well characterized. We assessed this by exposing endometrial stromal cells to hypoxia, which is a major cellular stress condition. We observed that hypoxia modifies the existing H3K4me3 marks and that promoter H3K4me3 breadth rather than height correlates with transcription. Broad H3K4me3 domains mark genes for endometrial core functions and are maintained or selectively extended upon hypoxia. Hypoxic extension of H3K4me3 breadth associates with stress adaptation genes relevant for the survival of endometrial cells including transcription factor KLF4, for which we found increased protein expression in the stroma of endometriosis lesions. These results substantiate the view on broad H3K4me3 as a marker of cell identity genes and reveal participation of H3K4me3 extension in cellular stress adaptation.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051620PMC
http://dx.doi.org/10.1016/j.isci.2022.104235DOI Listing

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  • The study reveals that these broad domains are dynamic during T cell differentiation and can distinguish between normal and cancerous cells, highlighting their association with oncogenes in T-ALL.
  • Findings suggest that targeting these broad H3K4me3 domains could be a potential strategy for prioritizing cancer-related gene regulation and treatment in leukemia.
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