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Enhancer adoption by an LTR retrotransposon generates viral-like particles causing developmental limb phenotypes

GSE246755 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 43 samples Submitted 2025/03/15 Platform GPL17021Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 43 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
43 samples: 14 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
Enhancer adoption by an LTR retrotransposon generates viral-like particles, causing developmental limb phenotypesNature genetics · 2025
Summary (written by the submitters)
Mammalian genomes are scattered with transposable elements (TEs). Silencing of TEs prevents harmful effects caused by either global activation leading to genome instability or insertional mutation disturbing gene transcription. However, whether the activation of a TE can be pathological without directly affecting gene expression is largely unknown.
Read the full summary ↓
Here, we show that a TE insertion can adopt nearby regulatory activity, producing cell-type-specific viral-like particles (VLPs) in the embryo and affecting organ formation. Failure to silence an LTR retrotransposon inserted upstream of the Fgf8 gene results in their co-expression during development. VLPs assembly in the Fgf8-expressing cells of the developing limb triggers apoptotic cell death, resulting in a limb malformation resembling human ectrodactyly. We rescued this phenotype with mutations in the retrotransposon coding sequence, preventing its full endogenous retroviral cycle. Our findings illustrate how TE insertion is incorporated into the local genomic regulatory landscape and show that VLP production in post-implantation embryos can be pathological.
Published in
Enhancer adoption by an LTR retrotransposon generates viral-like particles, causing developmental limb phenotypes
Glaser J, Cova G, Fauler B et al. · Nature genetics 2025 · PMID 40634706 · doi:10.1038/s41588-025-02248-5
This dataset
Open GSE246755 in finder → Find more mouse 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 GSE246755_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 PRJNA1034541 and SRA study SRP469646. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40634706) ↗
Study design
14 conditions, mostly in duplicate
4CMusD-Dac1J_Dac1JBl6_E12.5_FLHL ×3 4CMusD-Dac1J_Dac1J129sv_E12.5_FLHL ×3 cHiC_5LTR-LacZ_E11.5_FLHL ×3 RNAseq_WT129sv_E11.0_FL ×3 RNAseq_Dac1J129sv_E11.0_FL ×3 ChIPseq_CTCF_WT_E10.5_FLHL ×2 cHiC_Dac1JBl6_E11.5_FLHL ×2 cHiC_Dac1JBl6_E11.5_FLHL_tech ×2 +16 more

Supports a between-group comparison across 33 samples.

How we read this: 14 replicated groups read from 43 sample titles; they account for 33 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

+ 3 more — browse all 43 samples with per-sample file links →

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