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NFkB Signaling is Required for Xist RNA Localization at the Inactive X and for X-Chromosome Inactivation Maintenance Following T cell Activation [CUT&RUN]

GSE251879 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 14 samples Submitted 2024/10/29 Platform GPL30172
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 14 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
14 samples: 3 × Spleen, CD3 T cell, unstimulated, H2AK119Ub, biol vs 3 × Spleen, CD3 T cell, stimulated, H2AK119Ub, biol vs 3 × Spleen, CD3 T cell, unstimulated, H3K27me3, biol vs 3 × Spleen, CD3 T cell, stimulated, H3K27me3, biolGroups 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
Maintenance of X chromosome inactivation after T cell activation requires NF-κB signalingScience immunology · 2024
Summary (written by the submitters)
X Chromosome Inactivation (XCI) is a female-specific process which balances X-linked gene dosage between sexes. Unstimulated T cells lack cytological enrichment of Xist RNA and heterochromatic modifications on the inactive X chromosome (Xi), and these modifications become enriched at the Xi after cell stimulation. Here, we examined allele-specific gene expression and epigenomic profiling of the Xi following T cell stimulation.
Read the full summary ↓
We found that the Xi in unstimulated T cells is dosage compensated, and is enriched with the repressive H3K27me3 modification, but not H2AK119-ubiquitin (Ub) mark, including at promoters of XCI escape genes. Upon CD3/CD28 mediated T cell stimulation, the Xi accumulates H2AK119-Ub and H3K27me3 across the Xi. Next, we examined the T cell stimulation pathways responsible for Xist RNA localization to the Xi and found that T cell receptor (TCR) engagement, specifically NFkB signaling downstream of TCR, is required. Disruption of NFkB signaling, using inhibitors or genetic deletions, in mice and patients with immunodeficiencies prevents Xist/XIST RNA accumulation at the Xi and alters expression of some X-linked genes. Our findings reveal a novel connection between NFkB signaling pathways which impact XCI maintenance in female T cells.
Published in
Maintenance of X chromosome inactivation after T cell activation requires NF-κB signaling
Forsyth KS, Toothacre NE, Jiwrajka N et al. · Science immunology 2024 · PMID 39365876 · doi:10.1126/sciimmunol.ado0398
This dataset
Open GSE251879 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 GSE251879_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 PRJNA1055615 and SRA study SRP479557. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39365876) ↗
Study design
3 × Spleen, CD3 T cell, unstimulated, H2AK119Ub, biol vs 3 × Spleen, CD3 T cell, stimulated, H2AK119Ub, biol vs 3 × Spleen, CD3 T cell, unstimulated, H3K27me3, biol vs 3 × Spleen, CD3 T cell, stimulated, H3K27me3, biol

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 14 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
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