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Sirtuin 7 regulates dosage compensation and safeguards the female X-chromosome [RNA-seq_male_female_MEF]

GSE295586 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2026/04/07 Platform GPL34290
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 × MEF_Female_KO vs 3 × MEF_Female_WT vs 3 × MEF_Male_KO vs 3 × MEF_Male_WTGroups 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
SIRT7 regulates dosage compensation and safeguards the female X chromosomeNature · 2026
Summary (written by the submitters)
Sirtuins are deacetylases implicated in stress responses and longevity in mammals. Although their differential impact on the two sexes has been noted, underlying causes for sex biases in aging and cancer are not known. Here, using Sirtuin 7 (SIRT7) as a model in mice, we probe mechanisms leading to sex differences. We find that Sirt7-/- females have decreased fitness during embryogenesis and throughout life.
Read the full summary ↓
Intriguingly, SIRT7 preferentially localizes to the X-chromosome, suggesting a potential defect in X-inactivation — the arm of dosage compensation that equalizes X-chromosome expression between XX females and XY males. Indeed, SIRT7 ablation causes increased Xist RNA levels, H3K27me3 enrichment, and gene repression on the inactive X (Xi) chromosome. Surprisingly, however, loss of SIRT7 exerts greatest effects on the active X (Xa). In Sirt7-/- females, the Xa demonstrates 3D structural disorganization, increased chromatin mixing, and acute propensity to break and form chromosome fusions in an Xa-specific manner. Disproportional to autosomes and Xi, the Xa becomes super-acetylated on H3K36 and super-activated in gene expression, resulting in an imbalance in the 2nd arm of dosage compensation — known as “Xa-hyperactivation” — which evolved to balance X-linked gene expression against the genome. These data reveal a crosstalk between sirtuins and dosage compensation and identify a novel regulator of Xa-hyperactivation.
Published in
SIRT7 regulates dosage compensation and safeguards the female X chromosome
Simonet NG, Thackray JK, Kesner B et al. · Nature 2026 · PMID 42271055 · doi:10.1038/s41586-026-10645-x
This dataset
Open GSE295586 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 GSE295586_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 PRJNA1255220 and SRA study SRP581103. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42271055) ↗
Study design
3 × MEF_Female_KO vs 3 × MEF_Female_WT vs 3 × MEF_Male_KO vs 3 × MEF_Male_WT

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
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