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The Fosl1-Kdm6b Axis Controls Skeletal Muscle Fibrosis by Regulating Histone H3K27me3 [Cut&Tag]

GSE275142 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 24 samples Submitted 2025/02/28 Platform GPL23479
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 24 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
24 samples: 11 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)
Skeletal muscle fibrosis, characterized by the replacement of functional muscle tissue with fibrotic scarring, leads to muscle function loss and potentially fatal respiratory failure, particularly in muscular dystrophy. The mechanisms driving muscle fibrosis is not yet fully understood. Our study utilized single-cell RNA-seq and single-nuclei ATAC-seq to analyze the transcriptome and chromatin accessibility of regenerating and dystrophic skeletal muscle, identifying a specific subset of fibro-adipogenic precursors (FAPs) enriched in dystrophic muscles, termed fibrotic FAPs.
Read the full summary ↓
We further demonstrated that chronic inflammation upregulates Fosl1, an early response gene, which activates the expression of Kdm6b in fibrotic FAPs. Kdm6b, a histone demethylase, specifically removes the repressive histone H3K27me3 mark. Notably, targeting Kdm6b genetically and pharmacologically inhibits fibrotic di^erentiation in human and mouse FAPs in vitro and ameliorated muscle fibrosis in mouse models in vivo. Furthermore, constitutive activation of the Fosl1-Kdm6b pathway reduced H3K27me3 modification at critical fibrotic gene loci, leading to their transcriptional activation. Taken together, our findings reveal that chronic inflammation perpetuates the Fosl1-Kdm6b axis in FAPs, causing epigenomic reprogramming and altering the H3K27me3 landscape, which is essential for preventing fibrotic di^erentiation of FAPs and skeletal muscle fibrosis.
This dataset
Open GSE275142 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 GSE275142_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 PRJNA1149680 and SRA study SRP527291. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
11 conditions, mostly in duplicate
Mouse muscle Sca1+ FAP_H3K27me3_Mdx_CutNtag ×3 Mouse muscle Sca1+ FAP_H3K27me3_WT_CutNtag ×3 Mouse muscle Sca1+ FAP_Fosl1-CutNtag_Mdx ×2 Mouse muscle Sca1+ FAP_Fosl1-CutNtag_Utrn-Mdx ×2 Mouse muscle Sca1+ FAP_Fosl1-CutNtag_WT ×2 Mouse muscle Sca1+ FAP_H3K27me3_Utrn-Mdx_CutN… ×2 Mouse muscle Sca1+ FAP_H3K27me3-CutNtag_Pdgfr… ×2 Mouse muscle Sca1+ FAP_H3K27me3-CutNtag_Pdgfr… ×2 +3 more

Supports a between-group comparison across 24 samples.

How we read this: 11 replicated groups read from 24 sample titles; they account for 24 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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