GEO series

SP1 antagonizes H3K27me3 to shape chromatin landscapes for RNA polymerase II recruitment during gastrulation

GSE269652 Homo sapiens; Mus musculus Genome binding/occupancy profiling by high throughput sequencing 106 samples Submitted 2026/03/19 Platform GPL24247Platform GPL16791Platform GPL17021

Summary

Following implantation, the epiblast undergoes gastrulation to form the three germ layers, a process requiring precise temporal control of developmental gene expression. However, the mechanisms governing RNA polymerase II (Pol II) engagement at developmental gene promoters during this critical stage remain poorly understood. Here, we present a genome-wide analysis of Pol II occupancy in mouse post-implantation embryos, revealing that nearly half of bivalent promoters are bound by Pol II in a lineage-specific and temporally ordered manner. This recruitment follows a stepwise chromatin remodeling cascade, with initial deposition of H3K27me3, followed by H3K4me3 acquisition and Pol II engagement. Through genetic perturbation, we show that KMT2B promotes Pol II loading via H3K4me3 deposition, whereas the Polycomb component EED restricts this process by maintaining H3K27me3. Notably, we identify the transcription factor SP1 as a critical facilitator of Pol II recruitment at bivalent loci. SP1 binding coincides with reduced H3K27me3 levels and enhanced Pol II occupancy, and its loss leads to chromatin re-silencing and transcriptional failure. Together, our findings establish a chromatin-based regulatory framework in which SP1 and histone modifications cooperatively license the transcriptional activation of developmental genes during germ layer formation.

Published in

Shen X, Wen Y, Tang X et al. · Nucleic acids research 2026 · PMID 41978266 · doi:10.1093/nar/gkag305

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Direct links to NCBI, no account and no request form: the whole study as GSE269652_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 106 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 PRJNA1123158 and SRA study SRP513377. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41978266) ↗

Study design

17 conditions, mostly in duplicate

E6.5 Epiblast,Pol2,ChIP, ×3 E6.5 Extra-embryonic ectoderm,Pol2,ChIP, ×3 E6.5 Epiblast,Eed ko,Pol2,ChIP, ×2 E6.5 Epiblast,Eed Ctr,Pol2,ChIP, ×2 E6.5 Extra-embrynic ectoderm,Eed ko,Pol2,ChIP, ×2 E6.5 Epiblast,Jarid2 ko,Pol2,ChIP, ×2 E6.5 Epiblast,Jarid2 Ctr,Pol2,ChIP, ×2 E6.5 Extra-embrynic ectoderm,Jarid2 ko,Pol2,C… ×2 +13 more

Supports a between-group comparison across 36 samples.

17 replicated groups read from the first 40 of 106 sample titles; they account for 36 of them. Check it against the sample list below before relying on it.

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