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Genome-wide H3K4me3 profiling of circulating immune cells reveals dynamic epigenetic reprogramming during acute critical COVID-19

GSE339365 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 120 samples Submitted 2026/08/05 Platform GPL21697
Summary
Severe COVID-19 is associated with innate immune dysregulation resembling sepsis-induced immunoparalysis. Epigenetic mechanisms, particularly changes in H3K4me3 enrichment at gene promoters, have been observed in immune tolerance and monocyte dysfunction in sepsis. Whether comparable H3K4me3 alterations occur during acute critical COVID-19 illness has not been investigated. Among 706 differentially bound consensus peaks with promoter association between ICU and non-ICU groups, 704 showed increased H3K4me3 occupancy in ICU patients, predominantly at neutrophil effector gene loci, supported by pathway enrichment of neutrophil degranulation and innate immune activation. Monocyte HLA-DR expression and ex vivo TLR-stimulated IL-6 secretion were persistently reduced throughout the first week of ICU treatment. Longitudinal profiling in the ICU group revealed a shift from an interferon-driven chromatin signature at admission toward sustained innate immune activation and ECM remodelling at day seven. This study provides the first genome-wide H3K4me3 characterization of circulating immune cells during acute critical COVID-19, demonstrating that epigenetic reprogramming is an active and dynamic process that mirrors the functional immune dysregulation observed in these patients.
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Direct links to NCBI, no account and no request form: the whole study as GSE339365_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 120 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1498531 and SRA study SRP719950. Searching any of these in the dataset finder brings you back here.

Study design
38 conditions, each sampled once — no replicated groups
ICU patient #11, timepoint 1, ChIP with H3Pan… ×2 ICU patient #12, timepoint 1, ChIP with H3Pan… ×2

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