Mesoscale Modeling and Single-Nucleosome Tracking Reveal Remodeling of Clutch Folding and Dynamics in Stem Cell Differentiation

Nucleosomes form heterogeneous groups in vivo, named clutches. Clutches are smaller and less dense in mouse embryonic stem cells (ESCs) compared to neural progenitor cells (NPCs). Using coarse-grained modeling of the pluripotency Pou5f1 gene, we show that the genome-wide clutch differences between ESCs and NPCs can be reproduced at a single gene locus. Larger clutch formation in NPCs is associated with changes in the compaction and internucleosome contact probability of the Pou5f1 fiber. Using single-molecule tracking (SMT), we further show that the core histone protein H2B is dynamic, and its local mobility relates to the structural features of the chromatin fiber. H2B is less stable and explores larger areas in ESCs compared to NPCs. The amount of linker histone H1 critically affects local H2B dynamics. Our results have important implications for how nucleosome organization and H2B dynamics contribute to regulate gene activity and cell identity.

Authors: Pablo Aurelio Gómez-García, Stephanie Portillo-Ledesma, Maria Victoria Neguembor, Martina Pesaresi, Walaa Oweis, Talia Rohrlich, Stefan Wieser, Eran Meshorer, Tamar Schlick, Maria Pia Cosma, Melike Lakadamyali
Year of publication: 2021
Journal: Cell Reports, Volume 34, Issue 2, 2021, 108614, ISSN 2211-1247

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