Multiscale 3D Genome Rewiring during Mouse Neural Development.

Authors:
Boyan Bonev
Boyan Bonev
Institute of Human Genetics
San Francisco | United States
Netta Mendelson Cohen
Netta Mendelson Cohen
Weizmann Institute of Science
Israel
Lauriane Fritsch
Lauriane Fritsch
Université Paris-Sud
France
Giorgio L Papadopoulos
Giorgio L Papadopoulos
University of Crete
Gallos | Greece
Yaniv Lubling
Yaniv Lubling
Weizmann Institute of Science
Israel
Xiaole Xu
Xiaole Xu
Nantong University
China
Xiaodan Lv
Xiaodan Lv
BGI-Tech

Cell 2017 Oct;171(3):557-572.e24

Institute of Human Genetics, UMR 9002 of the CNRS and the Université de Montpellier, 34396 Montpellier, France. Electronic address:

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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Multi-scale 3D genome rewiring during mouse neural development

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Source
http://dx.doi.org/10.1016/j.cell.2017.09.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651218PMC

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October 2017
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