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

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

Cell Rep

Perelman School of Medicine, Department of Physiology, University of Pennsylvania, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA; Perelman School of Medicine, Department of Cell and Developmental Biology, University of Pennsylvania, Biomedical Research Building, 421 Curie Boulevard, Philadelphia, PA 19104, USA. Electronic address:

Published: January 2021

AI Article Synopsis

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842188PMC
http://dx.doi.org/10.1016/j.celrep.2020.108614DOI Listing

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