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Noncanonical PRC2 chromatin association reveals a key role of EZHIP in intergenerational epigenetic memory transition [ChIP-Seq, Cut & Run]

GSE289642 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 107 samples Submitted 2025/11/18 Platform GPL28330
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 107 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
107 samples: 45 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
EZHIP restricts noncanonical PRC2 binding and regulates H3K27me3 intergenerational inheritance and reprogrammingCell stem cell · 2025
Summary (written by the submitters)
Epigenetic memory undergoes drastic reprogramming in intergenerational gamete-to-embryo transition. H3K27me3, a histone mark catalyzed by PRC2 (Polycomb Repressive Complex 2), is an evolutionally conserved histone mark that plays essential roles in stably repressing developmental genes to maintain cell-type-specific programs. In mice, H3K27me3-mediated epigenetic memory, however, undergoes both resetting at classic Polycomb targets and inheritance of broad H3K27me3 domains that mediate noncanonical imprinting (noncanonical H3K27me3 domains) during early embryogenesis.
Read the full summary ↓
How such erasure and inheritance are achieved simultaneously remains elusive. Here, through temporal profiling of chromatin occupancy, we show that PRC2 associates with H3K27me3 at both Polycomb targets and noncanonical domains in growing oocytes. PRC2 then pre-disassembles and dissociates from chromatin in mature oocytes, before H3K27me3 erasure at Polycomb targets after fertilization. PRC2 reappears at Polycomb targets in blastocysts when H3K27me3 initiates restoration. By contrast, noncanonical H3K27me3 domains persist to blastocysts, where PRC2 rapidly rebinds by the end of 1-cell embryos until blastocysts. Mechanistically, we found that such noncanonical PRC2 action is regulated by EZHIP, a PRC2 inhibitory factor. By doing so, EZHIP plays a key role in both H3K27me3 erasure and intergenerational inheritance, as well as H3K27me3 re-establishment. Ezhip is highly translated around fertilization, which strongly restricts PRC2 activity, leading to gradual decrease of H3K27me3. Upon knockout of maternal Ezhip, PRC2 becomes hyperactive, binds promiscuously in the genome and deposits widespread H3K27me3. Consequently, H3K27me3 allelic bias and noncanonical imprinting, including imprinted X chromosome inactivation, are impaired. Unexpectedly, the widespread ectopic H3K27me3 paradoxically causes de-repression of H3K27me3 targets, possibly due to dilution of H3K27me3 effectors. Loss of Ezhip further attenuates H3K27me3 restoration at Polycomb targets during peri-implantation, and leads to gene dysregulation and sub-lethality after implantation. Taken together, we uncover PRC2 noncanonical chromatin association during the parental-to-embryonic transition and identify Ezhip as a crucial regulator for both erasure and inheritance of intergenerational epigenetic memories.
Published in
EZHIP restricts noncanonical PRC2 binding and regulates H3K27me3 intergenerational inheritance and reprogramming
Zeng Y, Kong F, Xu Z et al. · Cell stem cell 2025 · PMID 41118764 · doi:10.1016/j.stem.2025.09.009
This dataset
Open GSE289642 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE289642_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 PRJNA1223868 and SRA study SRP564000. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41118764) ↗
Study design
45 conditions, mostly in duplicate
WT_2C_EED ×2 WT_Bl_EED ×2 WT_D14_Ezh2 ×2 WT_FGO_Ezh2 ×2 WT_PN5_Ezh2 ×2 WT_2C_Ezh2 ×2 WT_Bl_Ezh2 ×2 WT_E6.5Epi_Ezh2 ×2 +54 more

Supports a between-group comparison across 90 samples.

How we read this: 45 replicated groups read from 107 sample titles; they account for 90 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

+ 67 more — browse all 107 samples with per-sample file links →

Datasets on a similar topic

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