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Cell. 2017 Oct 19;171(3):557-572.e24. doi: 10.1016/j.cell.2017.09.043.

Multiscale 3D Genome Rewiring during Mouse Neural Development.

Author information

1
Institute of Human Genetics, UMR 9002 of the CNRS and the Université de Montpellier, 34396 Montpellier, France. Electronic address: boyan.bonev@igh.cnrs.fr.
2
Weizmann Institute of Science, Rehovot 76100, Israel.
3
Institute of Human Genetics, UMR 9002 of the CNRS and the Université de Montpellier, 34396 Montpellier, France.
4
BGI, Shenzhen, 518083 Shenzhen, China.
5
INSERM U1051, Institute for Neurosciences, Hôpital Saint Eloi, Université de Montpellier 2, 34090 Montpellier, France.
6
Institute of Human Genetics, UMR 9002 of the CNRS and the Université de Montpellier, 34396 Montpellier, France. Electronic address: giacomo.cavalli@igh.cnrs.fr.

Abstract

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.

KEYWORDS:

3D genome architecture; Hi-C; Polycomb; cortical development; enhancers; neural differentiation; transcription; transcription factors

PMID:
29053968
PMCID:
PMC5651218
DOI:
10.1016/j.cell.2017.09.043
[Indexed for MEDLINE]
Free PMC Article

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