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Histone H3.3 chaperone HIRA is required for acquired tolerance by rendering stress-responsive genes poised for prospective lethal stresses [ChIP-seq]

GSE253873 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2024/10/15 Platform GPL11154
Summary
Appropriate responses to environmental challenges are imperative for the survival of all living organisms. Exposure to low-dose stresses is recognized to yield increased cellular fitness, a phenomenon termed hormesis. However, our molecular understanding of how cells respond to low-dose stress remains profoundly limited. Here we report that histone variant H3.3-specific chaperone, HIRA, is required for acquired tolerance, where low-dose heat stress exposure confers resistance to subsequent lethal heat stress. We found that human HIRA activates stress-responsive genes, including HSP70, by depositing histone H3.3 following low-dose stresses. These genes are also marked with histone H3 Lys-4 trimethylation and H3 Lys-9 acetylation, both active chromatin markers. Moreover, depletion of HIRA greatly diminished acquired tolerance, both in normal diploid fibroblasts and in HeLa cells. Collectively, our study revealed that HIRA is required for eliciting adaptive stress responses under environmental fluctuations and is a master regulator of stress tolerance.
Published in
Histone H3.3 chaperone HIRA renders stress-responsive genes poised for prospective lethal stresses in acquired tolerance
Nagagaki Y, Kozakura Y, Mahandaran T et al. · Genes to cells : devoted to molecular & cellular mechanisms 2024 · PMID 38977420 · doi:10.1111/gtc.13140
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Direct links to NCBI, no account and no request form: the whole study as GSE253873_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1067601 and SRA study SRP485224. Searching any of these in the dataset finder brings you back here.

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