GEO series

H3K9 di-methylation dynamics underlies mouse minor zygotic genome activation [spike-in ChIP-seq of mESC]

GSE297574 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 64 samples Submitted 2026/04/19 Platform GPL34290

Summary

Minor zygotic genome activation (ZGA) is crucial for early development and totipotency acquisition, yet the regulatory mechanisms driving minor ZGA genes remain elusive. Here we show that dynamic regulation of H3K9me2 is essential for minor ZGA. H3K9me2 levels at minor ZGA gene loci are reduced at early 2-cell and are re-established by morula. Maternal depletion of the H3K9 demethylases KDM3A and KDM3B leads to increased H3K9me2 and impaired minor ZGA in early 2-cell, followed by developmental arrest at 2- to 4-cell. In mESCs, H3K9 at minor ZGA loci is highly di-methylated; combined loss of the H3K9 methyltransferases G9a and SETDB1 leads to synergistic de-repression of minor ZGA genes. Mechanistically, SETDB1 specifically targets Dux, while G9a broadly represses minor ZGA genes through H3K9 di-methylation linked to lamina-associated heterochromatin formation. These findings establish H3K9me2 dynamics as a key regulator for minor ZGA, highlighting the indispensable role of epigenetic control in early embryogenesis.

Published in

Dynamic regulation of H3K9 dimethylation drives mouse minor zygotic genome activation

Maeda R, Kuroki S, Shimojo H et al. · Nature structural & molecular biology 2026 · PMID 42191875 · doi:10.1038/s41594-026-01811-w

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Direct links to NCBI, no account and no request form: the whole study as GSE297574_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 64 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1265210 and SRA study SRP586419. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42191875) ↗

Study design

16 conditions, mostly in triplicate

mESC_33-6_NT_control_H3K9me2_spike-in_lot ×3 mESC_33-6_NT_control_Input_spike-in_lot ×3 mESC_33-6_OHT_Setdb1-KO_H3K9me2_spike-in_lot ×3 mESC_33-6_OHT_Setdb1-KO_Input_spike-in_lot ×3 mESC_SG_NT_G9a-KO_H3K9me2_spike-in_lot ×3 mESC_SG_NT_G9a-KO_Input_spike-in_lot ×3 mESC_SG_OHT_G9a;Setdb1-DKO_H3K9me2_spike-in_l… ×3 mESC_SG_OHT_G9a;Setdb1-DKO_Input_spike-in_lot ×3 +8 more

Supports a between-group comparison across 40 samples.

16 replicated groups read from the first 40 of 64 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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