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Pre-occupied ATF4 relies on CEBPγ co-binding for robust transcription activation during integrated stress response [C2C12_Thap_RNA-seq]

GSE303803 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/09/09 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
12 samples: 3 × Ctrl-DMSO vs 3 × Ctrl-Thap vs 3 × Sh2-DMSO vs 3 × Sh2-ThapGroups 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)
Upon encountering stress, cells need to rapidly and extensively remodel their transcriptome to restore homeostasis and ensure survival. However, the molecular mechanisms underlying stress-induced transcriptional remodeling are not well understood. In this study, we employed multi-omics approaches to comprehensively profile the changes in transcriptome, epigenetic landscapes, and 3D genome organization during the integrated stress response (ISR), a conserved cellular pathway activated by diverse stress stimuli.
Read the full summary ↓
Our findings reveal that widespread transcriptional changes occur 4-6 hours after the induction of ISR, coinciding with the genome-wide binding of key transcriptional effector ATF4. Notably, while ATF4 binds to most of its target genes only upon ISR activation, it also occupies the promoters of hundreds of genes under non-stress conditions, priming them for enhanced transcriptional activation in response to stress signals. We further demonstrate that ATF4-mediated gene activation does not rely on traditional transcriptional regulatory mechanisms, such as increased H3K27 acetylation, chromatin accessibility, or remodeling of enhancer-promoter loops. Instead, our data suggest that the nuclear localization of ATF4 induces a pronounced genomic redistribution of transcriptional factor CEBP-γ, from non-ATF4 sites to a subset of ATF4-bound regions, where it collaborates with ATF4 to elicit transcriptional activation. The combined occupancy of ATF4 and CEBP-γ ultimately dictates the transcriptional outcomes during ISR. Interestingly, the preferred binding sites of CEBP-γ in response to stress are not determined by the strength of the CEBP-γ or ATF4 motifs, but rather by the higher-order chromatin architecture surrounding the binding sites. These findings provide novel insights into the molecular mechanisms that govern the rapid and efficient transcriptional remodeling during ISR, with potential implications for other stress responses.
This dataset
Open GSE303803 in finder → Find more mouse RNA-seq 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 GSE303803_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1297712 and SRA study SRP604051. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × Ctrl-DMSO vs 3 × Ctrl-Thap vs 3 × Sh2-DMSO vs 3 × Sh2-Thap

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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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