GEO series

The nucleolar granular component is required for NAD association with nucleoli and the establishment of repressive chromatin architecture [CHIPSeq_H3K9me2uponNPM1KD]

GSE270569 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2025/05/22 Platform GPL24247

Summary

Repressive chromatin domains often localize to the nuclear lamina or nucleolus. Although nucleolar-associated domains (NADs) have recently been mapped, their mechanisms of nucleolar association and functional significance remain unclear. Here, we show that nucleophosmin (NPM1), a factor located in the granular component of the nucleolus, mediates NAD association in mouse embryonic stem cells. NPM1 binds NADs, interacts with the histone methyltransferase G9a (EHMT2), and is required for establishing H3K9me2 at NADs. Loss of NPM1 or expression of a DNA-binding-deficient mutant disrupts NAD-nucleolus association and reduces H3K9me2 specifically at NADs. G9a is dispensable for NAD-nucleolus contacts, indicating that H3K9me2 is acquired after NADs associate with NPM1 at nucleoli. These findings reveal mechanistic insights into how genomic domains associate with nucleoli and form repressive chromatin and indicate that the nucleolus not only serves as a scaffold for positioning repressive domains but also plays a direct role in establishing their repressive chromatin states.

Published in

The nucleolar granular component mediates genome-nucleolus interactions and establishes their repressive chromatin states

Gupta S, Bersaglieri C, Bär D et al. · Molecular cell 2025 · PMID 40412390 · doi:10.1016/j.molcel.2025.05.004

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Also filed as BioProject PRJNA1127517 and SRA study SRP515875. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40412390) ↗

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