GEO series

A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis

GSE275221 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 3 samples Submitted 2025/06/06 Platform GPL30173

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 3 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)
Topic: Endometrial cancerThis series is part of our curated briefing on it.
Samples: 3 samples
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)

Functional inactivation of tumor suppressor genes drives cancer initiation, progression, and treatment responses. Most tumor suppressor genes are inactivated through one of two well-characterized mechanisms: DNA-level mutations such as point mutations or deletions, and promoter DNA hypermethylation. Here, we report a distinct third mechanism of tumor suppressor inactivation based on alterations to the histone rather than DNA code.

Read the full summary ↓

We demonstrated that PAX2 is an endometrial tumor suppressor recurrently inactivated by a distinct epigenetic reprogramming event in >80% of human endometrial cancers. Integrative transcriptomic, epigenomic, 3D genomic, and machine learning analyses showed that PAX2 transcriptional downregulation is associated with replacement of open/active chromatin features (H3K27ac/H3K4me3) with inaccessible/repressive chromatin features (H3K27me3) in a framework dictated by 3D genome organization. The spread of the repressive H3K27me3 signal resembled a pearl necklace with its length modulated by cohesin loops, thereby preventing transcriptional dysregulation of neighboring genes. This mechanism, involving the loss of a promoter-proximal super-enhancer, underlied transcriptional silencing of PAX2 in human endometrial cancers. Mouse and human preclinical models established PAX2 as a potent endometrial tumor suppressor. Functionally, PAX2 loss promoted endometrial carcinogenesis by rewiring the transcriptional landscape via global enhancer reprogramming. The discovery that most endometrial cancers originate from a recurring epigenetic alteration carries profound implications for their diagnosis and treatment.

This dataset

Open GSE275221 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Endometrial cancer landscape →

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 GSE275221_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 PRJNA1149833 and SRA study SRP527390. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 3 more — browse all 3 samples with per-sample file links →

More Endometrial cancer datasets

GSE275223 A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis 20 samples same disease briefing · shares pax2, carcinogenesis, reprogramming, endometrial, epigenetic, initiates, distinct, silences
GSE275222 A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis 14 samples same disease briefing · shares pax2, carcinogenesis, reprogramming, endometrial, epigenetic, initiates, distinct, silences
GSE294692 A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis 4 samples same disease briefing · shares pax2, carcinogenesis, reprogramming, endometrial, epigenetic, initiates, distinct, silences
GSE212217 Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti–PD-1 Immunotherapy in Endometrial Carcinoma 104 samples same disease briefing · shares endometrial, distinct
GSE272263 Adipocyte induced distinct gene expression profiling of human endometrioid endometrial cancer cells upon SIRT1 inhibition. 5 samples same disease briefing · shares endometrial, distinct
GSE319248 Histone Demethylase KDM4A Activates ERRγ-Dependent Cell Cycle Progression to Promote Endometrial Cancer Progression 4 samples same disease briefing · shares endometrial
GSE312323 Identification of genomic features that uniquely impact estrogen receptor alpha binding and its effects on gene expression in endometrial cancer [SOX17_ChIPseq] 2 samples same disease briefing · shares endometrial
GSE307568 Patient-derived organoid – immune cell co-culture platform for therapeutics discovery in high-grade endometrial cancer 189 samples same disease briefing · shares endometrial

Search all human ChIP / ATAC / CUT&Tag datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.