Work

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

Year: 2025

Type: article

Abstract: 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.

Source: Molecular Cell

DOI: 10.1016/j.molcel.2025.05.004

Authors: Shivani Gupta, Cristiana Bersaglieri, Dominik Bär, Mathieu Raingeval, Luana Schaab, Raffaella Santoro

Institutions: University of Zurich, Life Science Zurich

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $10,400

Funders: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Swiss Cancer Research Foundation, European Research Council, HORIZON EUROPE European Research Council