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Bonev, B. ; Mendelson Cohen, N.* ; Szabo, Q.* ; Fritsch, L.* ; Papadopoulos, G.L.* ; Lubling, Y.* ; Xu, X.* ; Lv, X.* ; Hugnot, J.P.* ; Tanay, A.* ; Cavalli, G.*

Multiscale 3D genome rewiring during mouse neural development.

Cell 171, 557-572.e24 (2017)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo. Additionally, we discovered long-range contacts between gene bodies of exon-rich, active genes in all cell types. During neural differentiation, contacts between active TADs become less pronounced while inactive TADs interact more strongly. An extensive Polycomb network in stem cells is disrupted, while dynamic interactions between neural transcription factors appear in vivo. Finally, cell type-specific enhancer-promoter contacts are established concomitant to gene expression. This work shows that multiple factors influence the dynamics of chromatin interactions in development.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 3d Genome Architecture ; Hi-c ; Polycomb ; Cortical Development ; Enhancers ; Neural Differentiation ; Transcription ; Transcription Factors
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Quellenangaben Volume: 171, Issue: 3, Pages: 557-572.e24 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)