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Nucleosome dynamics of human iPSC during neural differentiation

Harwood, Janet C, Kent, Nicholas A, Allen, Nicholas D and Harwood, Adrian J 2019. Nucleosome dynamics of human iPSC during neural differentiation. EMBO reports 20 (6) , e46960. 10.15252/embr.201846960

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Abstract

Nucleosome positioning is important for neurodevelopment, and genes mediating chromatin remodelling are strongly associated with human neurodevelopmental disorders. To investigate changes in nucleosome positioning during neural differentiation, we generate genome‐wide nucleosome maps from an undifferentiated human‐induced pluripotent stem cell (hiPSC) line and after its differentiation to the neural progenitor cell (NPC) stage. We find that nearly 3% of nucleosomes are highly positioned in NPC, but significantly, there are eightfold fewer positioned nucleosomes in pluripotent cells, indicating increased positioning during cell differentiation. Positioned nucleosomes do not strongly correlate with active chromatin marks or gene transcription. Unexpectedly, we find a small population of nucleosomes that occupy similar positions in pluripotent and neural progenitor cells and are found at binding sites of the key gene regulators NRSF/REST and CTCF. Remarkably, the presence of these nucleosomes appears to be independent of the associated regulatory complexes. Together, these results present a scenario in human cells, where positioned nucleosomes are sparse and dynamic, but may act to alter gene expression at a distance via the structural conformation at sites of chromatin regulation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Biosciences
Publisher: Nature Publishing Group: EMBO
ISSN: 1469-221X
Date of First Compliant Deposit: 17 April 2019
Date of Acceptance: 2 April 2019
Last Modified: 09 Jul 2019 09:22
URI: http://orca-mwe.cf.ac.uk/id/eprint/121838

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