GEO series

Distinct histone 3 lysine methylation states underlie tumor immune surveillance

GSE341379 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 50 samples Submitted 2026/07/27 Platform GPL30172

Summary

Mutations in histone 3 at or near lysine 36 (H3K36) have dominantly acting oncogenic effects in multiple tumor types by limiting H3K36-directed methyltransferases. Paradoxically, we find that expression of the H3K36M oncohistone unexpectedly inhibits tumor formation in KRAS-driven lung adenocarcinoma by inducing a potent immune-mediated tumor clearance. Mechanistically, oncohistone expression derepresses endogenous retroviral element transcription, results in the accumulation of double-stranded RNA (dsRNA), and activates an innate antiviral-like immune response that eradicates tumor growth. Surprisingly, while inactivation of the H3K36 di-methyltransferase NSD2 replicated all effects of oncohistone expression, inactivation of the H3K36 tri-methyltransferase SETD2 abolished element derepression and all associated downstream anti-cancer effects that are induced by oncohistone expression. These observations restructure our understanding of the roles of H3K36 methylation, the consequences of its deregulation in cancer, and shape our expectations for therapeutic interventions targeting H3K36 methyltransferases.

This dataset

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Direct links to NCBI, no account and no request form: the whole study as GSE341379_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 50 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1266719 and SRA study SRP636349. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

17 conditions, mostly in duplicate

mouse lung adenocarcinoma cell line, KP-Ctrl,… ×3 mouse lung adenocarcinoma cell line, KP-Setd2… ×3 mouse lung adenocarcinoma cell line, KP-H3K36… ×3 mouse lung adenocarcinoma cell line, KP-H3K36… ×3 KP-Ctrl, H3K36me2, biol ×2 KP-Setd2KO, H3K36me2, biol ×2 KP-H3K36M-Ctrl, H3K36me2, biol ×2 KP-H3K36M-Setd2KO, H3K36me2, biol ×2 +11 more

Supports a case/control comparison: 6 samples read as cases, 13 as controls.

17 replicated groups read from the first 40 of 50 sample titles; they account for 38 of them. Check it against the sample list below before relying on it.

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