GEO series

Dominant negative effects of Weaver syndrome-associated EZH2 variants [RNA-seq]

GSE302602 Mus musculus (mouse) RNA-seq (gene expression) 54 samples Submitted 2025/09/03 Platform GPL34290

At a glance

RNA-seq (gene expression) · mouse · 54 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 54 samples: 18 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: Dominant-negative effects of Weaver syndrome-associated EZH2 variantsGenes & development · 2025

Summary (written by the submitters)

Heterozygous missense mutations in EZH2 cause Weaver syndrome (WS), a developmental disorder characterized by intellectual disability and overgrowth. EZH2 encodes the enzymatic subunit of Polycomb Repressive Complex 2 (PRC2), which mediates mono-, di-, and tri-methylation of histone H3 lysine 27 (H3K27me1/2/3). Most WS-associated EZH2 variants lack functional characterization but are presumed loss of function.

Read the full summary ↓

However, the lack of early truncating mutations in EZH2 led us to hypothesise a dominant-negative mechanism for WS, which was supported by our structural analysis of all known WS-associated EZH2 variants. We isogenically modelled 10 representative variants in embryonic stem cells and showed they reduce global H3K27me2/3 with concomitant increases in H3K27ac and chromatin decompaction. Notably, the pattern of H3K27me2/3 reductions indicated dominant- negative interference on PRC2 activity, even when WS-variants were expressed at low levels. RNA-seq identified weakly Polycomb-bound genes that lose canonical PRC1 (cPRC1) occupancy and become derepressed, including several phenotypically relevant growth control genes. Comparative analysis of a gain-of-function EZH2 variant causing growth restriction revealed reciprocal chromatin and transcriptional changes compared to WS-associated variants. Taken together, our findings support a model where EZH2 variants associated with opposing developmental growth syndromes affect not only H3K27me3, but also intergenic H3K27me2, chromatin architecture, and cPRC1 recruitment.

Published in

Dominant-negative effects of Weaver syndrome-associated EZH2 variants

Deevy O, Li J, Monger C et al. · Genes & development 2025 · PMID 40846643 · doi:10.1101/gad.351884.124

This dataset

Open GSE302602 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 GSE302602_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1291488 and SRA study SRP600830. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40846643) ↗

Study design

18 conditions, mostly in triplicate

mESC_EZH2-A733T mutant, ×3 mESC_parental_EZH2-heterozygote, ×3 mESC_EZH2-R679C mutant, ×3 mESC_EZH2-K634E mutant, ×3 mESC_EZH2-K563E mutant, ×3 mESC_EZH2-A677T mutant, ×3 mESC_EZH2-Y728 mutant, ×3 mESC_EZH2-WT, ×3 +10 more

Supports a case/control comparison: 39 samples read as cases, 6 as controls.

How we read this: 18 replicated groups read from 54 sample titles; they account for 54 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

GSM9107350 mESC_EZH2-A733T mutant, rep1 mESC_EZH2-A733T mutant,
GSM9107351 mESC_EZH2-A733T mutant, rep2 mESC_EZH2-A733T mutant,
GSM9107352 mESC_EZH2-A733T mutant, rep3 mESC_EZH2-A733T mutant,
GSM9107353 mESC_parental_EZH2-heterozygote, rep1 mESC_parental_EZH2-hete…
GSM9107354 mESC_parental_EZH2-heterozygote, rep2 mESC_parental_EZH2-hete…
GSM9107355 mESC_parental_EZH2-heterozygote, rep3 mESC_parental_EZH2-hete…
GSM9107356 mESC_EZH2-R679C mutant, rep1 mESC_EZH2-R679C mutant,
GSM9107357 mESC_EZH2-R679C mutant, rep2 mESC_EZH2-R679C mutant,
GSM9107358 mESC_EZH2-R679C mutant, rep3 mESC_EZH2-R679C mutant,
GSM9107359 mESC_EZH2-K634E mutant, rep1 mESC_EZH2-K634E mutant,
GSM9107360 mESC_EZH2-K634E mutant, rep2 mESC_EZH2-K634E mutant,
GSM9107361 mESC_EZH2-K634E mutant, rep3 mESC_EZH2-K634E mutant,
GSM9107362 mESC_EZH2-K563E mutant, rep1 mESC_EZH2-K563E mutant,
GSM9107363 mESC_EZH2-K563E mutant, rep2 mESC_EZH2-K563E mutant,
GSM9107364 mESC_EZH2-K563E mutant, rep3 mESC_EZH2-K563E mutant,
GSM9107365 mESC_EZH2-A677T mutant, rep1 mESC_EZH2-A677T mutant,
GSM9107366 mESC_EZH2-A677T mutant, rep2 mESC_EZH2-A677T mutant,
GSM9107367 mESC_EZH2-A677T mutant, rep3 mESC_EZH2-A677T mutant,
GSM9107368 mESC_EZH2-Y728 mutant, rep1 mESC_EZH2-Y728 mutant,
GSM9107369 mESC_EZH2-Y728 mutant, rep2 mESC_EZH2-Y728 mutant,
GSM9107370 mESC_EZH2-Y728 mutant, rep3 mESC_EZH2-Y728 mutant,
GSM9107371 mESC_EZH2-WT, rep1 mESC_EZH2-WT,
GSM9107372 mESC_EZH2-WT, rep2 mESC_EZH2-WT,
GSM9107373 mESC_EZH2-WT, rep3 mESC_EZH2-WT,
GSM9107374 mESC_parental, rep1 mESC_parental,
GSM9107375 mESC_parental, rep2 mESC_parental,
GSM9107376 mESC_parental, rep3 mESC_parental,
GSM9107377 mESC_EZH2-A733T mutant, ATRA treated, rep1 mESC_EZH2-A733T mutant,…
GSM9107378 mESC_EZH2-A733T mutant, ATRA treated, rep2 mESC_EZH2-A733T mutant,…
GSM9107379 mESC_EZH2-A733T mutant, ATRA treated, rep3 mESC_EZH2-A733T mutant,…
GSM9107380 mESC_parental_EZH2-heterozygote, ATRA treated, rep1 mESC_parental_EZH2-hete…
GSM9107381 mESC_parental_EZH2-heterozygote, ATRA treated, rep2 mESC_parental_EZH2-hete…
GSM9107382 mESC_parental_EZH2-heterozygote, ATRA treated, rep3 mESC_parental_EZH2-hete…
GSM9107383 mESC_EZH2-R679C mutant, ATRA treated, rep1 mESC_EZH2-R679C mutant,…
GSM9107384 mESC_EZH2-R679C mutant, ATRA treated, rep2 mESC_EZH2-R679C mutant,…
GSM9107385 mESC_EZH2-R679C mutant, ATRA treated, rep3 mESC_EZH2-R679C mutant,…
GSM9107386 mESC_EZH2-K634E mutant, ATRA treated, rep1 mESC_EZH2-K634E mutant,…
GSM9107387 mESC_EZH2-K634E mutant, ATRA treated, rep2 mESC_EZH2-K634E mutant,…
GSM9107388 mESC_EZH2-K634E mutant, ATRA treated, rep3 mESC_EZH2-K634E mutant,…
GSM9107389 mESC_EZH2-K563E mutant, ATRA treated, rep1 mESC_EZH2-K563E mutant,…

+ 14 more — browse all 54 samples with per-sample file links →

Datasets on a similar topic

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GSE291454 A conserved function of EZH2-PRC2 in the repression of primitive endoderm cell fate [RNA-Seq - mouse] 22 samples shares ezh2, rna-seq
GSE296986 EZH2 alters aggressive variant prostate cancer subtype evolution, but is not required for neuroendocrine prostate cancer. [scRNA-seq] 17 samples shares ezh2, rna-seq
GSE279346 Ezh2 Delays Activation of Differentiation Genes During Normal Cerebellar Granule Neuron Development and in Medulloblastoma [RNA-seq] 15 samples shares ezh2, rna-seq
GSE298836 Loss of Histone Methyltransferase Ezh2 Exacerbates Polarization of Macrophages toward M2-Like Phenotypes by Hepatocellular Carcinoma [RNA-Seq] 14 samples shares ezh2, rna-seq
GSE269740 The role of EZH2 in sepsis-induced acute lung injury [RNA-Seq] 12 samples shares ezh2, rna-seq
GSE254325 Epigenetic regulation of chromosomal instability by EZH2 methyltransferase [RNA-seq] 12 samples shares ezh2, rna-seq
GSE278314 Cryptic splice sites generate heterogeneous EZH2 isoforms with distinct functions in embryonic development [RNA-seq] 12 samples shares ezh2, rna-seq

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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.