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Thyroid cancer-associated EZH1 Q571R mutation drives chromatin compaction and H3K27me3 invasion into active chromatin

GSE294323 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 18 samples Submitted 2026/07/03 Platform GPL34284Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 18 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
Thyroid cancerThis series is part of our curated briefing on it.
Samples
18 samples: 8 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.
Summary (written by the submitters)
Dysregulation of Polycomb Repressive Complex 2 (PRC2) contributes to cancer. Of its catalytic subunits, Enhancer of Zeste (EZH) 1 and EZH2, EZH2 mutations are extensively studied, but the role of EZH1 in cancer remains largely unexplored. Here, we investigate the thyroid cancer-associated EZH1 Q571R mutation and uncover a mechanism that extends beyond catalytic gain of function.
Read the full summary ↓
Using biochemical, single-molecule, epigenomic, and transcriptomic analyses, we demonstrated that EZH1 Q571R significantly enhances chromatin compaction and stimulates PRC2-EZH1 catalytic activity, thereby rewiring PRC2 chromatin interactions. This altered engagement enables PRC2 activity within H3K36me2-marked chromatin typically refractory to H3K27 methylation, leading to widespread epigenetic and transcriptional reprogramming. Notably, enhanced chromatin compaction is observed with EZH1 Q571R but not with the corresponding EZH2 Q570R mutation, indicating an EZH1-specific mechanism. Functionally, EZH1 Q571R accelerated tumor growth in vivo and induced pronounced micronuclei formation ex vivo, reflecting aberrant chromatin compaction and genome instability. Together, our study demonstrates that EZH1 Q571R promotes a permissive epigenomic landscape for the progression of follicular thyroid cancer.
This dataset
Open GSE294323 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Thyroid 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 GSE294323_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 PRJNA1249026 and SRA study SRP578008. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
8 conditions, mostly in duplicate
Nthy, EZH1 WT, CUT&Tag, HK27me3, ×2 Nthy, EZH1 WT, CUT&Tag, HK36me2, ×2 Nthy, EZH1 Q571R, CUT&Tag, HK27me3, ×2 Nthy, EZH1 Q571R, CUT&Tag, HK36me2, ×2 Nthy, EZH1 Y727D, CUT&Tag, H3K27me3, ×2 Nthy, EZH1 Q571R;Y727D, CUT&Tag, H3K27me3, ×2 Nthy, EZH2 WT, CUT&Tag, H3K27me3, ×2 Nthy, EZH2 Q570R, CUT&Tag, H3K27me3, ×2 +2 more

Supports a between-group comparison across 16 samples.

How we read this: 8 replicated groups read from 18 sample titles; they account for 16 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
More Thyroid cancer datasets

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