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

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Item Type:Article
Title:Genomic rewiring of SOX2 chromatin interaction network during differentiation of ESCs to postmitotic neurons
Creators Name:Bunina, D. and Abazova, N. and Diaz, N. and Noh, K.M. and Krijgsveld, J. and Zaugg, J.B.
Abstract: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.
Keywords:Multi-Omics, Transcription Factors, Neuronal Differentiation, Gene Regulation, Sox2, Atrx, Data Integration, Animals, Mice
Source:Cell Systems
Publisher:Cell Press / Elsevier
Page Range:480-494
Date:24 June 2020
Official Publication:https://doi.org/10.1016/j.cels.2020.05.003
PubMed:View item in PubMed

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