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Oxidative Stress Converts Benign Lesions to Cancer via a Self-Amplifying NRF2-EZH2 Loop [ATACseq_ChIPseq_RNAseq]

GSE214190 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 35 samples Submitted 2025/02/20 Platform GPL21103
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 35 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Mus musculus (mouse)
Samples
35 samples: 14 conditions, mostly in duplicateGroups 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.
Paper
Self-amplifying NRF2-EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancerNature cancer · 2025
Summary (written by the submitters)
Whether oxidative stress (OxS) acts mutationally or epigenetically to increase cancer risk is unknown. Pancreatic ductal carcinoma (PDAC) evolves from benign, low-grade PanIN (pancreatic intraepithelial neoplasia) lesions that frequently express oncogenic KRAS. Postulating that known risk factors convert benign PanIN to malignant progenitors via OxS and epigenetic mechanisms, we established a novel system to test this hypothesis.
Read the full summary ↓
Transient incubation of organoids, derived from pancreata with KrasG12D-induced low-grade PanIN, with H2O2 triggered irreversible malignant conversion mediated by an epigenetic network composed of NRF2, its direct transcriptional target EZH2, and EZH2-interacting transcription factors. Pharmacological or genetic activation of this network, maintained by a single NRF2 site in the EZH2 promoter, also triggered rapid malignant conversion and upregulation of malignancy-supportive metabolic genes that remained elevated in established PDAC.
Published in
Self-amplifying NRF2-EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer
Antonucci L, Li N, Duran A et al. · Nature cancer 2025 · PMID 40588523 · doi:10.1038/s43018-025-01003-3
This dataset
Open GSE214190 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 GSE214190_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA884338 and SRA study SRP399634. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40588523) ↗
Study design
14 conditions, mostly in duplicate
WT7dCeru_P ×4 KRas3dControl_P ×3 Krascells_ATAC_Control_Clone ×2 Krascells_ATAC_EzhKO_Clone ×2 Krascells_ChIP_H3K27ac_Control_Clone ×2 Krascells_ChIP_H3K27ac_EzhKO_Clone ×2 Krascells_ChIP_H3K4me3_Control_Clone ×2 Krascells_ChIP_H3K4me3_EzhKO_Clone ×2 +10 more

Supports a between-group comparison across 31 samples.

How we read this: 14 replicated groups read from 35 sample titles; they account for 31 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
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