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H2BE113K mutation promotes breast cancer metastasis through modulating chromatin dynamics

GSE295336 Homo sapiens; Mus musculus Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 77 samples Submitted 2026/05/20 Platform GPL24676Platform GPL24247
Summary
Cancer progression is driven by the accumulation of DNA mutations and aberrant gene regulation. Recent studies have demonstrated that multiple mutations in genes encoding histone H3 serve as drivers of tumorigenesis. However, the role and significance of various cancer-associated histone H2B mutations in cancer development remain largely unknown. Here, we investigate H2BE113K, a missense mutation of histone H2B predominantly found in breast cancer patients. Using MDA-MB-231 cells knockin with H2BE113K, we show that H2BE113K promotes colony formation in breast cancer. Of note, transcriptomic analysis reveals differential expression of genes in various cancer pathways in H2BE113K mutant cells. Intriguingly, the loci with elevated gene expression display increased chromatin accessibility and accompany with the enrichment of E113K mutant H2B. Importantly, the depletion of G3BP2, one of the H2BE113K target genes that has been implicated in breast cancer, reduces the colony formation phenotype in H2BE113K mutant cells. In addition, MMTV-PyMT breast cancer model crossbred with our H2BE113K knock-in mice results in elevated lung metastasis. Together, our findings provide critical insights in the mechanistic role of H2BE113K in gene regulation, chromatin function and breast cancer progression.
Published in
H2BE113K mutation promotes breast cancer metastasis through modulating chromatin dynamics
Hu 胡诗曼 S, Liu J, Zhou J et al. · Science advances 2026 · PMID 42430466 · doi:10.1126/sciadv.adx4982
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Also filed as BioProject PRJNA1254226 and SRA study SRP580537. Searching any of these in the dataset finder brings you back here.

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40 conditions, each sampled once — no replicated groups

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