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Profiling of gene expression, histone marks, chromatin accessibility, and DNA methylation in myeloid progenitors expressing H3WT, H3K4M, H3K27M, or H3K4M/K27M for 2 weeks [CUT&Tag]

GSE266188 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 36 samples Submitted 2025/07/17 Platform GPL30172
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 36 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
36 samples: 18 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
Bivalent chromatin instructs lineage specification during hematopoiesisCell · 2025
Summary (written by the submitters)
Developmental gene expression is tightly regulated by the dynamic interplay of H3K4 and H3K27 methylation associated with active and repressed genes, respectively. However, our understanding of the individual and combinatorial roles these histone modifications play in a physiological context remains incomplete. Here, we have leveraged histone mutant transgenic tools to uncover a previously unappreciated role for H3K4 methylation in adult hematopoiesis.
Read the full summary ↓
Adult mice globally depleted for all forms of H3K4 methylation via expression of an inducible histone H3 lysine-4-to-methionine (H3K4M) mutant allele succumbed to a severe loss of all major blood cell types. Unexpectedly however, H3K4M-expressing hematopoietic stem cells (HSCs) and committed progenitors were present at normal numbers and persisted long-term when transplanted into mice alongside unperturbed bone marrow, indicating that H3K4 methylation is dispensable for the maintenance and early commitment of HSCs but essential for the maturation of downstream progenitors. Importantly, the restoration of H3K4 methylation in H3K4M animals rescued their morbidity, released progenitors from the maturation block and enabled normal blood cell production. Mechanistically, we showed that H3K4 methylation opposes the deposition of repressive H3K27 methylation at differentiation-associated genes bivalently marked by H3K4me3 and H3K27me3 in HSCs or progenitors. Indeed, by concomitantly suppressing H3K27 methylation in H3K4 methylation-depleted mice we could rescue the acute lethality, hematopoietic failure and gene dysregulation. Collectively, our results reveal that H3K4 methylation safeguards hematopoiesis by opposing repressive H3K27 methylation at fate-instructive bivalent genes, providing evidence for the functional interaction between these crucial chromatin marks in mammalian tissue homeostasis.
Published in
Bivalent chromatin instructs lineage specification during hematopoiesis
Yagi M, Bonilla G, Hoetker MS et al. · Cell 2025 · PMID 40532700 · doi:10.1016/j.cell.2025.05.011
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 GSE266188_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 PRJNA1106174 and SRA study SRP504786. Searching any of these in the dataset finder brings you back here.

Study design
18 conditions, mostly in duplicate
H3K27ac H3K4M/K27M, ×2 H3K27me3 H3K4M/K27M, ×2 H3K4me1 H3K4M/K27M, ×2 H3K4me3 H3K4M/K27M, ×2 H3K27ac H3K27M, ×2 H3K27me3 H3K27M, ×2 H3K4me1 H3K27M, ×2 H3K4me3 H3K27M, ×2 +10 more

Supports a between-group comparison across 36 samples.

How we read this: 18 replicated groups read from 36 sample titles; they account for 36 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
Datasets on a similar topic

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