GEO series

A transcription regulator atlas identifies TOX3 as an Atoh1 co-activator in cerebellar development and tumorigenesis

GSE312658 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 13 samples Submitted 2026/03/18 Platform GPL24247Platform GPL21273

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 13 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: 13 samples: 5 × Cerebellum_Ctrl vs 5 × Cerebellum_cKOGroups 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: A transcription regulator atlas identifies TOX3 as an Atoh1 coactivator in cerebellar development and tumorigenesisProceedings of the National Academy of Sciences of the United States of America · 2026

Summary (written by the submitters)

Organ development and function are orchestrated by intricate transcriptional circuits. Here, we present a comprehensive atlas profiling 1,904 transcription regulators in the brain, cerebellum, heart, kidney, liver, ovary, and testis of fetal, neonatal and adult mice. Using this dataset, we uncover TOX High Mobility Group Box Family Member 3 (TOX3) as a potential co-activator of Atoh1 in cerebellar granule neuron progenitors.

Read the full summary ↓

Tox3-deficient mice display severe ataxia and cerebellar hypoplasia, driven by depletion of granule neuron progenitors, diminished Atoh1 expression, and impaired primary cilia. Single-nucleus RNA-seq analyses reveals compromised maintenance of the progenitor pool. TOX3 is also highly expressed in subsets of medulloblastoma, and its deletion reduces cerebellar neoplasia and prolongs survival in a mouse model. Mechanistically, how lineage-defining factors such as Atoh1 drive robust gene expression despite weak intrinsic transactivation activity remains unclear. We show that Tox3 physically associates with Atoh1 and co-occupies shared regulatory elements, converting an otherwise weak single-copy Atoh1-reponsive E-box into a highly active enhancer that drives transcriptional activation by up to 120-fold, including at an ultra-conserved E-box downstream of Atoh1 itself. Cross-species single-cell comparisons further show an association between Tox3 expression and cerebellum expansion during vertebrate evolution. Together, this work supports Tox3 as a critical Atoh1 co-activator in cerebellar development, tumorigenesis and evolution, while providing an atlas and screening strategy as a valuable resource for exploring novel transcriptional regulators in organogenesis and tissue physiology.

Published in

A transcription regulator atlas identifies TOX3 as an Atoh1 coactivator in cerebellar development and tumorigenesis

Chen X, Zhong X, Yue W et al. · Proceedings of the National Academy of Sciences of the United States of America 2026 · PMID 41849381 · doi:10.1073/pnas.2527163123

This dataset

Open GSE312658 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 GSE312658_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 PRJNA1375660. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41849381) ↗

Study design

5 × Cerebellum_Ctrl vs 5 × Cerebellum_cKO

Supports a between-group comparison across 10 samples.

How we read this: 2 replicated groups read from 13 sample titles; they account for 10 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

GSM9350894 Cerebellum_Ctrl_1 Cerebellum_Ctrl
GSM9350895 Cerebellum_Ctrl_2 Cerebellum_Ctrl
GSM9350896 Cerebellum_Ctrl_3 Cerebellum_Ctrl
GSM9350897 Cerebellum_cKO_1 Cerebellum_cKO
GSM9350898 Cerebellum_cKO_2 Cerebellum_cKO
GSM9350899 Cerebellum_cKO_3 Cerebellum_cKO
GSM9350909 Ctrl_cerebellum
GSM9350910 cKO_cerebellum
GSM9352257 Cerebellum_Ctrl3 Cerebellum_Ctrl
GSM9352258 Cerebellum_cKO1 Cerebellum_cKO
GSM9352259 Cerebellum_Ctrl1 Cerebellum_Ctrl
GSM9352260 Cerebellum_cKO2 Cerebellum_cKO
GSM9352261 Cerebellum_Input

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