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TET Proteins Control Early-Stage Stem Cell Differentiation via H3K27me3, Not DNA Demethylation

GSE242461 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 30 samples Submitted 2026/08/01 Platform GPL30172Platform GPL21626
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 30 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
30 samples: 11 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.
Summary (written by the submitters)
TET proteins reportedly have dual functions as mediators of DNA demethylation and H3K27me3 deposition in embryonic stem cells (ESCs) and during differentiation. To further explore the role of TET proteins in early ESC differentiation, we conducted mapping experiments on wild-type and cells lacking all three TET proteins (TET-TKO) at three stages: in ESCs, immediately after exit from pluripotency, and at the early differentiation stage.
Read the full summary ↓
We observed minimal differences in transcriptional and DNA methylation levels between wild-type and TET-TKO cells during ESCs and after exit from pluripotency. However, H3K27ac sequential chromatin immunoprecipitation followed by sequencing (ChIP-seq) and bisulfite-seq and single-cell RNA-seq maps demonstrated that during differentiation TET-TKO cells lost their ability to activate the differentiation to extraembryonic endoderm (XEN). This inability was not due solely to higher levels of DNA methylation, as enhancers that were unaffected by TET also showed higher levels of DNA methylation. Loss of XEN differentiation was associated with reduced levels of H3K27me3 during the pluripotency stage. We were able to rescue the effect of TET deficiency by co-culturing TET-TKO ESCs with wild-type ESCs. The co-culturing approach restored XEN differentiation, even though TET proteins were absent during differentiation. We propose that DNA demethylation catalyzed by TET proteins is of minimal importance during the initial stages of differentiation. Instead, the key regulatory function of TETs lies in establishing the ESC ground state through H3K27me3 chromatin deposition.
This dataset
Open GSE242461 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 GSE242461_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 PRJNA1013518 and SRA study SRP458846. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
11 conditions, mostly in duplicate
H3K27Ac day2 WT ×2 H3K27Ac day2 TET-TKO ×2 H3K27Ac day5 WT ×2 H3K27Ac day5 TET-TKO ×2 scRNAseq day2 WT ×2 scRNAseq day2 TET-TKO ×2 scRNAseq day5 WT ×2 scRNAseq day5 TET-TKO ×2 +11 more

Supports a between-group comparison across 22 samples.

How we read this: 11 replicated groups read from 30 sample titles; they account for 22 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
Datasets on a similar topic

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