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Unbalanced chromatin binding of Polycomb complexes drives neurodevelopmental disorders [CUT&RUN]

GSE286290 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 81 samples Submitted 2026/02/17 Platform GPL34284Platform GPL34290
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 81 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
81 samples: 39 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
Unbalanced chromatin binding of Polycomb complexes drives neurodevelopmental disordersMolecular cell · 2026
Summary (written by the submitters)
Heterozygous de novo missense mutations in genes encoding Polycomb-group (PcG) proteins can cause diverse neurodevelopmental disorders (NDDs), but the underlying mechanisms are not yet understood. Here, we identified novel mutations in the two E3-ligases of the Polycomb Repressive complex 1 (PRC1), RING1 and RNF2, in individuals with NDDs and uncover distinct mechanisms by which PRC1 activity can be compromised.
Read the full summary ↓
Building on this, and as a proof of concept, we generated embryonic stem cells (ESCs) and a novel mouse model carrying a heterozygous Rnf2 allele with a mutation that produces a deleterious Ring1bR70H variant. This variant causes a cell fate change in neuroprecursors (NPCs) towards the non-neuronal lineages glial and microglia. Allele-specific profiling revealed that Ring1bR70H integrates into canonical PRC1, disrupting the balance of PRC1 complexes by displacing variant PRC1 from chromatin, resulting in PcG target genes upregulation. In mutant NPCs, we uncover an aberrant retention of PcG and chromatin compaction at key NPC pioneer factors and Wnt signaling genes. Critically, a heterozygous Rnf2 mutation in mice is sufficient to disrupt neural connectivity and structural organization in key brain regions, including the medial prefrontal cortex and hippocampus. Our findings establish Rnf2 as essential for neurodevelopmental integrity and brain function, shedding light on how PRC1 dysfunction contributes to NDDs.
Published in
Unbalanced chromatin binding of Polycomb complexes drives neurodevelopmental disorders
Borges RL, González-Blanco G, Arigela H et al. · Molecular cell 2026 · PMID 41653922 · doi:10.1016/j.molcel.2026.01.023
This dataset
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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 GSE286290_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 PRJNA1208536 and SRA study SRP556321. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41653922) ↗
Study design
39 conditions, mostly in duplicate
R70H mESC, allelM, HA, MA, ×2 R70H mESC, allelW, FL, MA, ×2 R70H mESC, H3K27me3, MA, ×2 R70H mESC, H3K27me3, MB, ×2 R70H mESC, Histone H2B ubiquitination, MA, ×2 R70H mESC, Histone H2B ubiquitination, MB, ×2 R70H mNPC, allelM, FL, MB, ×2 R70H mNPC, allelW, FL, MA, ×2 +34 more

Supports a between-group comparison across 78 samples.

How we read this: 39 replicated groups read from 81 sample titles; they account for 78 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

+ 41 more — browse all 81 samples with per-sample file links →

Datasets on a similar topic

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