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Stepwise de novo establishment of inactive X chromosome architecture in early development [XEN cells RNA-seq]

GSE206179 Mus musculus (mouse) RNA-seq (gene expression) 32 samples Submitted 2024/09/10 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 32 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
32 samples: 13 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
Stepwise de novo establishment of inactive X chromosome architecture in early developmentNature genetics · 2024
Summary (written by the submitters)
X chromosome inactivation (XCI) triggers a drastic reprogramming of gene activities and chromosome architecture. However, how the 3D organization of the inactive X chromosome (Xi) is de novo established in vivo in mammals remains poorly understood. By comprehensive stage- and lineage- specific Hi-C mapping, we identified a unique Xist-separated megadomain structure (X-megadomains) on the Xi in mouse early embryos.
Read the full summary ↓
X-megadomains emerge in extraembryonic lineages during imprinted XCI, in derived extraembryonic endoderm (XEN) cells, and transiently in the embryonic lineages during random XCI, before Dxz4-delineated megadomains (D-megadomains) occur at later stages in a strain-specific manner. Mechanistically, the emergence of X-megadomain boundary coincides with developmentally regulated enhancer activities and cohesin binding in a regulatory region near Xist (XRR). We pinpointed a subregion XRRa that is critical for the X-megadomain boundary. X-megadomains are impaired when XRRa is removed or cohesin is degraded in XEN cells. Importantly, this is accompanied by ectopic activation of regulatory elements and genes near Xist, suggesting that cohesin loading at regulatory elements promotes X-megadomains and confines local gene activities. Finally, the knockout of XRRa in mouse preimplantation embryos severely impairs the activation of Xist and the initiation of XCI. Hence, our data not only reveal stepwise chromosome folding during de novo XCI in vivo, but also support a model that regulatory element-dependent gene activation and cohesin loading simultaneously promote essential transcription activities and subsequent self-insulation amid global silencing during the early stage of XCI.
Published in
Stepwise de novo establishment of inactive X chromosome architecture in early development
Du Z, Hu L, Zou Z et al. · Nature genetics 2024 · PMID 39256583 · doi:10.1038/s41588-024-01897-2
This dataset
Open GSE206179 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 GSE206179_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 PRJNA849559 and SRA study SRP381865. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39256583) ↗
Study design
13 conditions, mostly in duplicate
RNA-seq XEN cells, XistpA, ×4 RNA-seq XEN cells, WT, ×3 RNA-seq XEN cells, XRRa KO, ×3 RNA-seq XEN cells, XRRb XaKO, ×2 RNA-seq XEN cells, XRRb XiKO, ×2 RNA-seq XEN cells, XRRc XaKO, ×2 RNA-seq XEN cells, XRRc XiKO, ×2 RNA-seq XEN cells, Rad21-degron, DMSO treated… ×2 +7 more

Supports a case/control comparison: 6 samples read as cases, 3 as controls.

How we read this: 13 replicated groups read from 32 sample titles; they account for 30 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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