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Preventing CpG hypermethylation in oocytes safeguards mouse development [Cut&Run]

GSE234967 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 17 samples Submitted 2025/03/27 Platform GPL19057
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 17 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
17 samples: 7 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
Preventing CpG hypermethylation in oocytes safeguards mouse developmentDevelopmental cell · 2025
Summary (written by the submitters)
DNA methylation (DNAme) controls gene expression, genome stability and cell identity in many mammalian organisms. Genomes of most somatic cells and spermatozoa are largely methylated, apart from CpG-dense sequences including gene promoters1. In mouse oocytes, DNAme is mostly limited to transcribed regions2,3. The mechanisms restricting global DNAme acquisition in developing oocytes and the relevance thereof for regulating gene expression and embryo development after fertilization are unknown.
Read the full summary ↓
Here we show that the histone H3 lysine 36 dimethyl (H3K36me2) demethylases KDM2A and KDM2B redundantly execute multiple chromatin functions during oocyte development, which are vital to pre- and post-implantation development. Firstly, by serving as recruitment factors of variant Polycomb Repressive Complex 1 (vPRC1), they control genome-wide H2A mono-ubiquitination deposition (H2AK119u1) and PRC1-dependent gene repression4. Secondly, as demethylases, KDM2A/KDM2B prevent global H3K36me2 accumulation, thereby impeding DNMT3A-catalyzed de novo DNAme within PRC1-controlled promoter, genic, and intergenic regions, and even at non-PRC1-controlled CpG-dense gene promoters5. Decisively, we demonstrate that aberrant Dnmt3a-dependent DNAme established in Kdm2a/Kdm2b double mutant oocytes represses transcription from maternal loci in two-cell embryos and impairs pre-implantation development. Hence, KDM2A/KDM2B are essential for defining the appropriate oocyte DNA methylome which in turn conveys competence for early embryonic development. Our research implies that the reprogramming capacity eminent to early embryos is insufficient to erase aberrant DNAme from maternal chromatin. Lastly, our work shows that early development is vulnerable to gene dosage haplo-insufficiency effects, possibly in a parental-specific manner.
Published in
Preventing CpG hypermethylation in oocytes safeguards mouse development
Kawamura YK, Ozonov EA, Papasaikas P et al. · Developmental cell 2025 · PMID 40902605 · doi:10.1016/j.devcel.2025.08.005
This dataset
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.

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 GSE234967_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA983817 and SRA study SRP443825. Searching any of these in the dataset finder brings you back here.

Study design
7 conditions, mostly in duplicate
GVO_H2AK119ub_Ctrl.Kdm2a_KO.Kdm2b_KO ×2 GVO_H2AK119ub_KO.Kdm2a_KO.Kdm2b_dCxxC ×2 GVO_H2AK119ub_KO.Kdm2a_KO.Kdm2b_KO ×2 GVO_H3K36me2_KO.Kdm2a_KO.Kdm2b_dCxxC ×2 GVO_H3K36me2_KO.Kdm2a_KO.Kdm2b_KO ×2 GVO_H3K36me3_Ctrl.Kdm2a_KO.Kdm2b_KO ×2 GVO_H3K36me3_KO.Kdm2a_KO.Kdm2b_KO ×2 GVO_H2AK119ub_Ctrl.Kdm2a_KO.Kdm2b_dCxxC ×1 +2 more

Supports a between-group comparison across 14 samples.

How we read this: 7 replicated groups read from 17 sample titles; they account for 14 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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