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Paraspeckle Protein NONO Regulates Active Chromatin by Allosterically Stimulating NSD1

GSE304363 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 36 samples Submitted 2025/08/20 Platform GPL24676Platform GPL24247Platform GPL16791
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 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
Mus musculus (mouse)
Samples
36 samples: 9 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.
Paper
Paraspeckle protein NONO regulates active chromatin by allosterically stimulating NSD1Cell reports · 2025
Summary (written by the submitters)
NSD1 is a key histone methyltransferase that catalyzes di-methylation of lysine 36 of histone H3 (H3K36me2), essential for active chromatin domains. While the loss of NSD1 activity halts embryonic development and its aberrant gain drives oncogenesis in leukemia and glioma, the regulatory mechanisms remain poorly understood. Here, we uncover that NSD1 requires allosteric activation through the aromatic pocket of its PWWP2 domain.
Read the full summary ↓
Surprisingly, NSD1-PWWP2 binds to a non-canonical target, nuclear paraspeckle protein NONO, and this protein-protein interaction allosterically stimulates NSD1. Mouse embryonic stem cells (mESC) engineered with mutations in the aromatic pocket of NSD1-PWWP2 cannot differentiate into neural progenitor cells (NPC), and genetic depletion of NONO partially phenocopied this defect, potentially explaining the neurodevelopmental disorder phenotypes in NSD1- and NONO-deficient diseases. Our work uncovered a mechanism driving active chromatin domain formation, an implication in the interplay between nuclear paraspeckles and active chromatin, and a vulnerability of NSD1 for therapeutic interventions.
Published in
Paraspeckle protein NONO regulates active chromatin by allosterically stimulating NSD1
Hsu CI, Mei S, Demmerle J et al. · Cell reports 2025 · PMID 40913772 · doi:10.1016/j.celrep.2025.116247
This dataset
Open GSE304363 in finder → Find more 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 GSE304363_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 PRJNA1301111 and SRA study SRP606242. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40913772) ↗
Study design
9 conditions, mostly in duplicate
WT ×2 WT+RA-D3 ×2 WT+RA-D6 ×2 NSD1-KO ×2 NSD1-KO+RA-D3 ×2 NSD1-KO+RA-D6 ×2 NONO-KO ×2 NONO-KO+RA-D3 ×2 +19 more

Supports a between-group comparison across 18 samples.

How we read this: 9 replicated groups read from 36 sample titles; they account for 18 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
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