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Targeting CDK7 function in the RNA Polymerase II transcription cycle in inflammatory arthritis [ChIP-seq]

GSE255372 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 69 samples Submitted 2025/01/29 Platform GPL24247Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 69 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
69 samples: 23 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
Disrupting the RNA polymerase II transcription cycle through CDK7 inhibition ameliorates inflammatory arthritisScience translational medicine · 2024
Summary (written by the submitters)
Macrophages are main drivers of inflammation and tissue damage in autoimmune diseases including rheumatoid arthritis. The rate-limiting step for transcription of >70% of inducible genes in macrophages is RNA Polymerase II (Pol II) promoter-proximal pause release, yet, the specific role of Pol II pausing in inflammation or whether it can be modulated therapeutically is unknown.
Read the full summary ↓
Genetic ablation of a pause-stabilizing negative elongation factor (NELF) in macrophages enhanced the transcriptional response of paused anti-inflammatory genes to LPS, followed by secondary attenuation of inflammatory signaling, and reduced severity of K/BxN-serum transfer (ST) arthritis in mice. To disrupt Pol II pause establishment pharmacologically, we employed covalent inhibitors of the TFIIH-associated cyclin-dependent kinase (CDK) 7, THZ1 and YKL-5-124. Both dramatically reduced Pol II pausing in murine and human macrophages, broadly suppressed induction of pro- but not anti-inflammatory genes, and rapidly reversed pre-established inflammatory macrophage polarization by TNF+IFNγ. In vivo, CDK7i ameliorated the acute K/BxN-ST and chronic progressive hTNF-transgenic arthritis in mice. Finally, CDK7i downregulated a pathogenic gene expression signature in synovial explants from arthritis patients. We propose that interfering with Pol II pausing by targeting CDK7 represents a novel therapeutic opportunity for inflammatory diseases.
Published in
Disrupting the RNA polymerase II transcription cycle through CDK7 inhibition ameliorates inflammatory arthritis
Chen X, Shibu G, Sokolsky BA et al. · Science translational medicine 2024 · PMID 39565872 · doi:10.1126/scitranslmed.adq5091
This dataset
Open GSE255372 in finder → Find more 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 GSE255372_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 PRJNA1074764 and SRA study SRP489034. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39565872) ↗
Study design
23 conditions, mostly in triplicate
KO_30m_LPS ×3 KO_60m_LPS ×3 KO_PBS ×3 WT_30m_LPS ×3 WT_60m_LPS ×3 WT_PBS ×3 DMSO_Polii ×3 DMSO_pPolii ×3 +23 more

Supports a between-group comparison across 61 samples.

How we read this: 23 replicated groups read from 69 sample titles; they account for 61 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

+ 29 more — browse all 69 samples with per-sample file links →

Datasets on a similar topic

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