GEO series

Crosstalk between the polycomb repressive complex 2 and DNA methylation mediates neuroendocrine prostate cancer lineage plasticity [RNA-Seq]

GSE289248 Mus musculus (mouse) DNA methylation 2 samples Submitted 2025/11/25 Platform GPL24247

At a glance

DNA methylation · mouse · 2 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Mus musculus (mouse)
Samples: 2 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.
Paper: Crosstalk between EZH2 and DNA methylation mediates neuroendocrine prostate cancer lineage plasticityNature communications · 2026

Summary (written by the submitters)

Acquired changes in DNA methylation have been proposed as a mechanism underlying epigenetic plasticity in several cancer types. In prostate cancer, methylation changes are dynamic, with preclinical studies pointing to a tumor suppressor role of the DNA methyltransferase DNMT1 in early stage, in contrast to an oncogenic function of DNMT1 in later stage.

Read the full summary ↓

The importance of DNA methylation dynamics during normal development and cell lineage fate decisions also points to DNA methylation having a critical function in lineage plasticity, yet the mechanisms by which DNA methylation changes drives lineage transitions in prostate cancer is not well understood. DNA methylation can directly repress gene expression but also cooperate with other epigenetic pathways to modulate downstream transcriptional activity. The enhancer of zeste homolog 2 (EZH2) protein is a subunit of the polycomb repressive complex 2 (PRC2) and catalyzer of the repressive histone 3 lysine 27 tri-methylation (H3K27me3) mark that also acts to suppress downstream transcriptional activity and has also been implicated in lineage plasticity. EZH2 is overexpressed in castration-resistant prostate cancer (CRPC) including NEPC and is an emerging therapeutic target. Although, the compensatory relationship between DNA methylation and EZH2 has been shown in embryonic stem cell studies and in some cancer types during acquired treatment resistance or immune evasion, how DNA methylation and EZH2/PRC2 interact to modulate prostate cancer lineage plasticity has not been characterized. In this study, we address the potential crosstalk between epigenetic pathways in advanced prostate cancer and demonstrate how DNA methylation and H3K27me3 profiles overlap and cooperate to reprogram the epigenome during prostate cancer lineage plasticity. Using both mouse and patient-derived models, we highlight the compensatory roles of these two repressive machineries during progression of CRPC towards a NE-lineage state. We predict their specific impact on NEPC progression by assessing the associated molecular alterations following genetic and pharmacological perturbations of each.

Published in

Crosstalk between EZH2 and DNA methylation mediates neuroendocrine prostate cancer lineage plasticity

Singh R, Venkadakrishnan VB, Imada E et al. · Nature communications 2026 · PMID 41720768 · doi:10.1038/s41467-026-69308-0

This dataset

Open GSE289248 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 GSE289248_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 beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1221996 and SRA study SRP563074. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41720768) ↗

Samples in this study

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

+ 2 more — browse all 2 samples with per-sample file links →

Datasets on a similar topic

GSE297143 EZH2 alters aggressive variant prostate cancer subtype evolution, but is not required for neuroendocrine prostate cancer [RNAseq] 54 samples shares neuroendocrine, prostate
GSE309033 Combined BET Bromodomain and DNMT Inhibition Targets Lineage Plasticity in Prostate Cancer [BETi_DNMTi_mouse_RNAseq] 51 samples shares plasticity, prostate
GSE293599 The Polycomb Protein EED Constrains the SCLC Neuroendocrine Phenotype and Drives Lung Cancer Histological Transformation [Bulk RNA-seq] 50 samples shares neuroendocrine, polycomb
GSE271053 A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer [RNA-Seq] 43 samples shares neuroendocrine, prostate
GSE247019 Cancer-associated DNA Hypermethylation of Polycomb Targets Requires DNMT3A Dual Recognition of histone H2AK119 Ubiquitination and the Nucleosome Acidic Patch 134 samples shares methylation, polycomb
GSE240971 UHRF2 mediates resistance to DNA methylation reprogramming in primordial germ cells 95 samples shares methylation, mediates
GSE297048 EZH2 alters aggressive variant prostate cancer subtype evolution, but is not required for neuroendocrine prostate cancer [ChIP-seq] 40 samples shares neuroendocrine, prostate
GSE242201 DNA methylation shapes the Polycomb landscape during the exit from naive pluripotency 39 samples shares methylation, polycomb

Search all mouse RNA-seq 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.