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Histone H4 lysine 20 tri-methylation safeguards breast cancer lineage fidelity and unfolded protein response [scRNA-seq]

GSE289192 Mus musculus (mouse) Single-cell RNA-seq 12 samples Submitted 2026/04/26 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 12 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism: Mus musculus (mouse)
Samples: 12 samples: 3 × 4T1_DMSO_Tumo vs 3 × 4T1_A196_Tumo vs 3 × EMT6_DMSO_Tumo vs 3 × EMT6_A196_TumoGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Triple-negative breast cancer (TNBC) is a breast cancer subtype with worse prognosis and limited therapeutic options, partly due to significant epigenetic heterogeneity both within and between tumors. We previously reported that histone H4 lysine 20 trimethylation (H4K20me3) is the most variable histone modification in TNBC. H4K20me3 showed an opposing genomic distribution to other H4 acetylations and was essential for histone integration with a subset of distal intergenic genomic regions.

Read the full summary ↓

Unlike H3K9me3, H4K20me3 exhibited greater heterogeneity across tumors and normal mammary glands. Regions uniquely enriched for H4K20me3 have higher epigenetic and transcriptional activity. Inhibition of the H4K20me3 methyltransferase, KMT5B/5C using A-196 led to substantial H4K20me3 loss and H4K20me1 gain at regions associated with lineage-specificity, stress response, and cell cycle regulation. A-196 treatment moderately suppressed tumor growth in vivo, inducing mesenchymal transition and unfolded protein response (UPR) in cancer cells, and increased proinflammatory macrophage infiltration into the tumor microenvironment. Integrated multi-omic analysis revealed that mesenchymal TNBCs, with the lowest H4K20me3 levels, have more active chromatin at UPR genes and stronger responses to ER stress inducers. Consistently, KMT5B/5C inhibition in basal TNBC induced mesenchymal-like features, heightened ER stress response and the associated cell proliferative suppression through increased G1 arrest, driven by the de novo recruitment of the transcriptional repressor E2F4. Combining A-196 with the HSP90 inhibitor 17AAG synergistically reduced TNBC tumor growth. Overall, our study identifies H4K20me3 as a facultative heterochromatin mark regulating lineage identity and UPR in TNBC, offering novel epigenetic therapeutic strategies targeting KMT5B/5C.

This dataset

Open GSE289192 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE289192_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1221885 and SRA study SRP562940. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

3 × 4T1_DMSO_Tumo vs 3 × 4T1_A196_Tumo vs 3 × EMT6_DMSO_Tumo vs 3 × EMT6_A196_Tumo

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8786162 4T1_DMSO_Tumor1 4T1_DMSO_Tumo
GSM8786163 4T1_DMSO_Tumor2 4T1_DMSO_Tumo
GSM8786164 4T1_DMSO_Tumor3 4T1_DMSO_Tumo
GSM8786165 4T1_A196_Tumor1 4T1_A196_Tumo
GSM8786166 4T1_A196_Tumor2 4T1_A196_Tumo
GSM8786167 4T1_A196_Tumor3 4T1_A196_Tumo
GSM8786168 EMT6_DMSO_Tumor1 EMT6_DMSO_Tumo
GSM8786169 EMT6_DMSO_Tumor2 EMT6_DMSO_Tumo
GSM8786170 EMT6_DMSO_Tumor3 EMT6_DMSO_Tumo
GSM8786171 EMT6_A196_Tumor1 EMT6_A196_Tumo
GSM8786172 EMT6_A196_Tumor2 EMT6_A196_Tumo
GSM8786173 EMT6_A196_Tumor3 EMT6_A196_Tumo

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