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Nrf2-mediated chromatin activation of hyperosmotic response genes attenuates heat-induced renal injury [ChIP-seq]

GSE266022 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 24 samples Submitted 2026/07/29 Platform GPL24247
Summary
The escalating frequency and duration of extreme weather events, driven by ongoing climate change, are heightening health hazards associated with heat stress. Heat stress can cause whole-body hyperosmolarity and increase risk of chronic kidney disease. Here, we confirmed Nrf2 as the core transcription factor for cellular resistance to hyperosmotic stress through drug screening. Meanwhile, we constructed a mouse model of renal injury caused by high temperature dehydration, genetic deletion of Nrf2 further increased the renal injury and fibrosis. The natural compound SFN, found in cruciferous plants, can be used to activate Nrf2 and alleviate kidney damage caused by high-temperature dehydration. Mechanistically, we performed hyperosmotic stress in kidney collecting duct cells, and through ATAC-seq and ChIP-seq analysis of multiple histone modifications, found that most of the hyperosmotic response genes changed their chromatin state after pharmacological activation of Nrf2. The activation of the chromatin state in hyperosmotic response genes enhances the binding affinity of Nfat5 following exposure to hyperosmotic stress. Together, activation of Nrf2 maintains the active chromatin state of hyperosmotic response genes. Under hyperosmotic stress, the core transcription factor Nfat5 efficiently activates gene expression, thereby assisting cells in resisting hyperosmotic stress. Additionally, activation of Nrf2 by SFN may serve as a potential therapeutic approach for preventing renal injury caused by high-temperature dehydration.
Published in
Nrf2-mediated epigenetic priming of osmoprotective genes enhances cellular adaptation to hyperosmotic stress
Lu Y, Li N, Dou X et al. · The Journal of biological chemistry 2026 · PMID 42331111 · doi:10.1016/j.jbc.2026.113278
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Direct links to NCBI, no account and no request form: the whole study as GSE266022_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 24 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1105358 and SRA study SRP504398. Searching any of these in the dataset finder brings you back here.

Study design
24 conditions, each sampled once — no replicated groups

Read from 24 sample titles: 24 distinct titles with little repetition. Check it against the sample list below before relying on it.

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