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Transcriptional and epigenetic rewiring by the NUP98::KDM5A fusion oncoprotein directly activates CDK12 (Cut&Tag)

GSE255802 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 20 samples Submitted 2025/02/17 Platform GPL30173Platform GPL30172
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 20 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
Acute myeloid leukemiaThis series is part of our curated briefing on it.
Samples
20 samples: 6 conditions, mostly in triplicateGroups 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
Transcriptional and epigenetic rewiring by the NUP98::KDM5A fusion oncoprotein directly activates CDK12Nature communications · 2025
Summary (written by the submitters)
Nucleoporin 98 (NUP98) fusion oncoproteins are strong drivers of pediatric acute myeloid leukemia (AML) with poor prognosis. Here we show that NUP98 fusion-expressing AML harbors an epigenetic signature that is characterized by increased accessibility of hematopoietic stem cell genes and enrichment of activating histone marks. We employ an AML model for ligand-induced degradation of the NUP98::KDM5A fusion oncoprotein to identify epigenetic programs and transcriptional targets that are directly regulated by NUP98::KDM5A through CUT&Tag and nascent RNA-seq.
Read the full summary ↓
Orthogonal genome-wide CRISPR/Cas9 screening identifies 12 direct NUP98::KDM5A target genes, which are essential for AML cell growth. Among these, we validate cyclin-dependent kinase 12 (CDK12) as a druggable vulnerability in NUP98::KDM5A-expressing AML. In line with its role in the transcription of DNA damage repair genes, small-molecule-mediated CDK12 inactivation causes increased DNA damage, leading to AML cell death. Altogether, we show that NUP98::KDM5A directly regulates a core set of essential target genes and reveal CDK12 as an actionable vulnerability in AML with oncogenic NUP98 fusions.
Published in
Transcriptional and epigenetic rewiring by the NUP98::KDM5A fusion oncoprotein directly activates CDK12
Troester S, Eder T, Wukowits N et al. · Nature communications 2025 · PMID 40389480 · doi:10.1038/s41467-025-59930-9
This dataset
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.

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 GSE255802_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1076553 and SRA study SRP489766. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
cutntag_DMSO_H3K27ac ×3 cutntag_DMSO_H3K4me3 ×3 cutntag_H3K27ac ×3 cutntag_H3K4me3 ×3 cutntag_dTAG13_H3K27ac ×3 cutntag_dTAG13_H3K4me3 ×3 cutntag_DMSO_IgG ×1 cutntag_IgG ×1

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 20 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
More Acute myeloid leukemia datasets

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