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CDK8 Inhibition Releases the Muscle Differentiation Blockade in Fusion-driven Alveolar Rhabdomyosarcoma [CUT&RUN]

GSE303151 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 50 samples Submitted 2026/06/12 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 50 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
Soft tissue sarcomaThis series is part of our curated briefing on it.
Samples
50 samples: 23 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)
Alveolar rhabdomyosarcoma (aRMS) is a fusion-driven pediatric cancer with poor survival and limited therapeutic options. To uncover novel vulnerabilities, we employed complex-based analysis of the functional genomic dataset (Depmap), identifying CDK8 as a novel dependency in aRMS. Both CDK8 knockout or pharmacologic inhibition impaired tumor cell growth and induced myogenic differentiation in vitro and in vivo.
Read the full summary ↓
Compared to genetic loss, CDK8 inhibition induced more dynamic transcriptional changes, suggesting a distinct gain-of-function mechanism of the CDK8 inhibitor. With a genome-scale CRISPR-Cas9 drug modifier screen, we determined that the maximal anti-tumor activity of the CDK8 inhibitor requires the presence of the Mediator kinase module and transcriptional cooperation with the SAGA complex. We further identified SIX4 as a key transcription factor mediating CDK8 inhibitor-induced transcriptional activation of myogenic differentiation genes and tumor cell proliferation. These findings establish a strong rationale for CDK8 inhibition as a differentiation-inducing therapeutic strategy in aRMS.
This dataset
Open GSE303151 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Soft tissue sarcoma 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 GSE303151_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 PRJNA1294235 and SRA study SRP602524. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
23 conditions, mostly in duplicate
C&R_Rh30-P3F-FKBP_P3F-HA_DMSO ×2 C&R_Rh30-P3F-FKBP_P3F-HA_BI1347-24hr ×2 C&R_Rh30-P3F-FKBP_P3F-HA_BI1347-72hr ×2 C&R_Rh30_SIX4_DMSO ×2 C&R_Rh30_SIX4_BI1347-24hr ×2 C&R_Rh30_SIX4_BI1347-72hr ×2 C&R_Rh30_TADA2B_DMSO ×2 C&R_Rh30_TADA2B_BI1347-24hr ×2 +19 more

Supports a between-group comparison across 46 samples.

How we read this: 23 replicated groups read from 50 sample titles; they account for 46 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

+ 10 more — browse all 50 samples with per-sample file links →

More Soft tissue sarcoma datasets

Search all human ChIP / ATAC / CUT&Tag datasets in GEO →

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