GEO series
Uncovering Critical Lysines in Mammalian Histone H3 with High-Throughput CRISPR Prime Editing [CUT&Tag]
GSE319420
Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
26 samples
Submitted 2026/05/09
Platform GPL30172
Summary
Histone proteins are central to regulating eukaryotic genomes, and their post-translational modifications play key roles in controlling gene expression, DNA repair and chromatin structure. Understanding the functions of individual histone modifications is a significant challenge in mammalian chromatin biology, primarily due to the multiple copies of histone genes found in mammalian genomes. In this study, we present a high-throughput CRISPR prime editing platform that allows for base-precise, combinatorial, and reversible mutagenesis of all canonical and non-canonical histone H3 genes within their native genomic context. Using this system, we systematically substituted each lysine residue in histone H3 with arginine and compared each mutation against synonymous lysine-to-lysine controls. This unbiased functional screen revealed a core set of lysines, including H3K4, H3K9, H3K14, H3K18, and H3K79, whose mutations impair cellular fitness in mouse embryonic stem cells, highlighting the critical roles of their post-translational modifications in chromatin function. In addition, our approach demonstrated that H3K56 acetylation, previously linked to genome stability in yeast and Drosophila, plays a conserved role in safeguarding the genome in mammalian cells. Extending this approach, we generated double histone H3 mutants to probe functional redundancy between several lysine residues. While individual substitutions caused minimal defects, specific combinations, most notably H3K27R+H3K36R, revealed impairments in stem cell self-renewal and distinct transcriptional consequences, uncovering regulatory crosstalk not evident from single-site perturbations. This study presents the first comprehensive functional map of histone H3 lysines in a mammalian system, establishing a broadly applicable platform for dissecting histone modifications with advanced precision.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE319420_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 26 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1423263 and SRA study SRP676849. Searching any of these in the dataset finder brings you back here.
Study design
10 conditions, mostly in triplicate
CnT_H3K18ac_H312K18K ×3
CnT_H3K18ac_H312K18 ×3
CnT_H3K18ac_H3123K18 ×3
CnT_H33_H312K18K ×3
CnT_H33_H312K18 ×3
CnT_H33_H3123K18 ×3
CnT_H3K36me3_K36K ×2
CnT_H3K36me3_K36 ×2
+2 more
Supports a between-group comparison across 26 samples.
10 replicated groups read from 26 sample titles; they account for 26 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9517610 CnT_H3K36me3_K36K_1
- GSM9517611 CnT_H3K36me3_K36K_2
- GSM9517612 CnT_H3K36me3_K36R_1
- GSM9517613 CnT_H3K36me3_K36R_2
- GSM9517614 K27me3_H3K27K_10_1
- GSM9517615 K27me3_H3K27K_10_2
- GSM9517616 K27me3_H3K27R_7_1
- GSM9517617 K27me3_H3K27R_7_2
- GSM9517618 CnT_H3K18ac_H312K18K_1
- GSM9517619 CnT_H3K18ac_H312K18K_2
- GSM9517620 CnT_H3K18ac_H312K18K_3
- GSM9517621 CnT_H3K18ac_H312K18R_1
- GSM9517622 CnT_H3K18ac_H312K18R_2
- GSM9517623 CnT_H3K18ac_H312K18R_3
- GSM9517624 CnT_H3K18ac_H3123K18R_1
- GSM9517625 CnT_H3K18ac_H3123K18R_2
- GSM9517626 CnT_H3K18ac_H3123K18R_3
- GSM9517627 CnT_H33_H312K18K_1
- GSM9517628 CnT_H33_H312K18K_2
- GSM9517629 CnT_H33_H312K18K_3
- GSM9517630 CnT_H33_H312K18R_1
- GSM9517631 CnT_H33_H312K18R_2
- GSM9517632 CnT_H33_H312K18R_3
- GSM9517633 CnT_H33_H3123K18R_1
- GSM9517634 CnT_H33_H3123K18R_2
- GSM9517635 CnT_H33_H3123K18R_3
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