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Glucocorticoid Receptor Suppresses GATA6-Mediated RNA Polymerase II Pause Release to Modulate Classical Subtype Identity in Pancreatic Cancer

GSE271731 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 36 samples Submitted 2025/01/07 Platform GPL30173
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 36 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
Homo sapiens (human)
Samples
36 samples: 12 conditions, mostly in triplicateGroups 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
Glucocorticoid receptor suppresses GATA6-mediated RNA polymerase II pause release to modulate classical subtype identity in pancreatic cancerGut · 2025
Summary (written by the submitters)
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a five-year survival rate of 12%. It has two major molecular subtypes: classical and basal, regulated by the master transcription factors (MTFs) GATA6 and ΔNp63, respectively. This study aims to uncover the transcriptional regulatory mechanisms controlling PDAC subtype identity.
Read the full summary ↓
We integrated primary tumor single-cell RNA-seq, patient-derived xenograft RNA-seq, and multispectral imaging to identify MTF-dependent, subtype-specific markers. We created subtype-specific fluorescent reporter systems and conducted drug screenings to find actionable targets. We analyzed genome-wide occupancy (ChIP-seq) for epigenetic status (H3K27ac), MTFs (GATA6, ΔNp63), RNA polymerase II (Pol II), nascent RNA capture sequencing (PRO-seq), and H3K4me3-anchored chromatin topology (HiChIP). Additionally, we used nuclease-dead Cas9 (dCas9) to manipulate transcriptional regulatory mechanisms. Our approach identified glucocorticoid receptor (GR) agonists as agents that suppress the classical transcriptional program by modulating GATA6 activity. GATA6 regulates classical-specific transcription through promoter-proximal pause (PPP) release. Depletion of GATA6 increased Pol II occupancy at GATA6-bound enhancers and transcriptional start sites, stabilizing enhancer-promoter interactions. Artificially inducing pausing at GATA6-bound enhancers with dCas9 abrogated target gene expression and induced pausing at both the enhancer and target gene promoter. Conversely, ΔNp63 in basal PDAC promotes Pol II recruitment and stabilizes enhancer-promoter interactions. This study provides new insights into the transcriptional control of PDAC subtypes and suggests potential therapeutic strategies, highlighting the role of glucocorticoids in PDAC chemotherapy.
Published in
Glucocorticoid receptor suppresses GATA6-mediated RNA polymerase II pause release to modulate classical subtype identity in pancreatic cancer
Ekstrom TL, Rosok RM, Abdelrahman AM et al. · Gut 2025 · PMID 39884837 · doi:10.1136/gutjnl-2024-334374
This dataset
Open GSE271731 in finder → Find more human ChIP / ATAC / CUT&Tag 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 GSE271731_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 PRJNA1131618 and SRA study SRP517903. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39884837) ↗
Study design
12 conditions, mostly in triplicate
AsPC1_ATAC ×3 L36pl_ATAC ×3 ATACseq_AsPC1_Ctrl ×3 ATACseq_AsPC1_siGATA6 ×3 ATACseq_AsPC1_BI653048 ×3 ATACseq_TCCPAN2_Ctrl ×3 ATACseq_TCCPAN2_siGATA6 ×3 ATACseq_TCCPAN2_BI653048 ×3 +4 more

Supports a between-group comparison across 36 samples.

How we read this: 12 replicated groups read from 36 sample titles; they account for 36 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
Datasets on a similar topic

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