GEO series

KAT6A Chimeras Forms a Self-Reinforcing Epigenetic Module with NURF and MLL/COMPASS in AML [ChIP-Seq]

GSE299381 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 13 samples Submitted 2025/06/24 Platform GPL24247

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: 11 distinct titles, 2 of them repeatedGroups 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: KAT6A chimeras form a self-reinforcing epigenetic module with NURF and MLL/COMPASS to sustain AMLGenome biology · 2025

Summary (written by the submitters)

KAT6A-CBP (K/C) and KAT6A-P300 (K/P) fusions are recurrent genetic alterations in acute myeloid leukemia(AML) that are associated with poor prognosis. The large size of these fusion proteins has posed challenges in developing preclinical models, limiting mechanistic studies. To address this, we employed a domain-focused truncation strategy to generate de novo murine models of K/C and K/P fusions, which faithfully recapitulate the morphological, immunophenotypic, and transcriptomic features of KAT6A-rearranged AML.

Read the full summary ↓

Genomic profiling revealed that KAT6A fusions preferentially localize to H3K4me2/3-marked regions and interact with the Nucleosome Remodeling Factor (NURF), a critical H3K4me2/3 reader. Disrupting NURF-chromatin interactions impaired K/C recruitment to target loci and disrupted MLL/COMPASS-mediated H3K4me2 deposition, thereby establishing an epigenetic regulatory module involving KAT6A chimeras, NURF, and MLL/COMPASS. Concurrently, CBP/P300 inhibition reduced histone acetylation, chromatin accessibility, and genomic targeting of the module. Therapeutically, NURF inhibition induced cell cycle arrest and suppressed leukemia proliferation, while CBP/P300 inhibition promoted leukemia differentiation. Both strategies demonstrated promising efficacy in K/C murine models, with superior effects observed with combined NURF and CBP/P300 inhibition. These findings uncover a self-reinforcing epigenetic module centered on histone reader proteins and modifying enzymes, providing mechanistic insights into KAT6A-rearranged AML and identifying promising combinatorial therapeutic vulnerabilities.

Published in

KAT6A chimeras form a self-reinforcing epigenetic module with NURF and MLL/COMPASS to sustain AML

Lv J, Yin Z, Li C et al. · Genome biology 2025 · PMID 40830799 · doi:10.1186/s13059-025-03743-y

This dataset

Open GSE299381 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE299381_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 PRJNA1274025 and SRA study SRP590877. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40830799) ↗

Study design

11 distinct titles, 2 of them repeated

ChIP-seq-MouseLeukemiaCells-BZ1-antiH3K4me ×2 ChIP-seq-MouseLeukemiaCells-DMSO-antiH3K4me ×2

How we read this: Read from 13 sample titles: 11 distinct titles with little repetition. 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

GSM9038327 ChIP-seq-MouseLeukemiaCells-A485-antiBPTF
GSM9038328 ChIP-seq-MouseLeukemiaCells-A485-antiMLL
GSM9038329 ChIP-seq-MouseLeukemiaCells-A485-antiPolII
GSM9038330 ChIP-seq-MouseLeukemiaCells-DMSO-antiBPTF
GSM9038331 ChIP-seq-MouseLeukemiaCells-DMSO-antiMLL
GSM9038332 ChIP-seq-MouseLeukemiaCells-DMSO-antiPolII
GSM9038333 ChIP-seq-MouseLeukemiaCells-BZ1-antiH3K4me1
GSM9038334 ChIP-seq-MouseLeukemiaCells-BZ1-antiH3K4me2
GSM9038335 ChIP-seq-MouseLeukemiaCells-BZ1-antiWDR5
GSM9038336 ChIP-seq-MouseLeukemiaCells-DMSO-antiH3K4me1
GSM9038337 ChIP-seq-MouseLeukemiaCells-DMSO-antiH3K4me2
GSM9038338 ChIP-seq-MouseLeukemiaCells-DMSO-antiWDR5
GSM9038339 ChIP-seq-MouseLeukemiaCells-BZ1-antiPolII

Datasets on a similar topic

GSE299382 KAT6A Chimeras Forms a Self-Reinforcing Epigenetic Module with NURF and MLL/COMPASS in AML [ATAC-Seq] 4 samples shares compass, kat6a, nurf, mll, aml, self-reinforcing, epigenetic, chimeras
GSE299379 KAT6A Chimeras Forms a Self-Reinforcing Epigenetic Module with NURF and MLL/COMPASS in AML [RNA-Seq] 35 samples shares compass, kat6a, nurf, mll, aml, self-reinforcing, epigenetic, chimeras
GSE249215 Non-Canonical PRC1.1 is required for the activity of Menin-MLL1 Inhibitors in NUP98-Rearranged AML [ChIP-Seq] 171 samples shares mll, aml
GSE311724 Effects of loss of KAT6A on histone acetylation and methylation levels, as well as MLL1 and POLR2A occupancy 134 samples shares kat6a, mll
GSE301680 MLL3 and MLL4 redundantly license HSC self-renewal and myeloid identity while opposing B-cell priming, independently of COMPASS enzymatic functions [ChIP II] 6 samples shares compass, mll
GSE301672 MLL3 and MLL4 redundantly license HSC self-renewal and myeloid identity while opposing B-cell priming, independently of COMPASS enzymatic functions [ChIP-seq I] 5 samples shares compass, mll
GSE301675 MLL3 and MLL4 redundantly license HSC self-renewal and myeloid identity while opposing B-cell priming, independently of COMPASS enzymatic functions [scATAC] 4 samples shares compass, mll
GSE249218 Non-Canonical PRC1.1 is required for the activity of Menin-MLL1 Inhibitors in NUP98-Rearranged AML 220 samples shares mll, aml

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