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Genomic rewiring of SOX2 chromatin interaction network during differentiation of ESCs to postmitotic neurons

Cellular differentiation requires dramatic changes in chromatin organization, transcriptional regulation, and protein production. To understand the regulatory connections between these processes, we generated proteomic, transcriptomic, and chromatin accessibility data during differentiation of mouse...

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Hauptverfasser: Bunina, Daria (VerfasserIn) , Abazova, Nadeshda (VerfasserIn) , Diaz, Nichole (VerfasserIn) , Noh, Kyung-Min (VerfasserIn) , Krijgsveld, Jeroen (VerfasserIn) , Zaugg, Judith B. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: June 17, 2020
In: Cell systems
Year: 2020, Jahrgang: 10, Heft: 6, Pages: 480-494, e1-e8
ISSN:2405-4720
DOI:10.1016/j.cels.2020.05.003
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cels.2020.05.003
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S2405471220301885
Volltext
Verfasserangaben:Daria Bunina, Nade Abazova, Nichole Diaz, Kyung-Min Noh, Jeroen Krijgsveld, and Judith B. Zaugg
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Zusammenfassung:Cellular differentiation requires dramatic changes in chromatin organization, transcriptional regulation, and protein production. To understand the regulatory connections between these processes, we generated proteomic, transcriptomic, and chromatin accessibility data during differentiation of mouse embryonic stem cells (ESCs) into postmitotic neurons and found extensive associations between different molecular layers within and across differentiation time points. We observed that SOX2, as a regulator of pluripotency and neuronal genes, redistributes from pluripotency enhancers to neuronal promoters during differentiation, likely driven by changes in its protein interaction network. We identified ATRX as a major SOX2 partner in neurons, whose co-localization correlated with an increase in active enhancer marks and increased expression of nearby genes, which we experimentally confirmed for three loci. Collectively, our data provide key insights into the regulatory transformation of SOX2 during neuronal differentiation, and we highlight the significance of multi-omic approaches in understanding gene regulation in complex systems.
Beschreibung:Gesehen am 10.08.2020
Beschreibung:Online Resource
ISSN:2405-4720
DOI:10.1016/j.cels.2020.05.003

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