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Multiscale 3D genome rewiring during mouse neural development.
Cell 171, 557-572.e24 (2017)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
3d Genome Architecture ; Hi-c ; Polycomb ; Cortical Development ; Enhancers ; Neural Differentiation ; Transcription ; Transcription Factors
ISSN (print) / ISBN
0092-8674
e-ISSN
1097-4172
Zeitschrift
Cell
Quellenangaben
Band: 171,
Heft: 3,
Seiten: 557-572.e24
Verlag
Cell Press
Verlagsort
Cambridge, Mass.
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Helmholtz Pioneer Campus (HPC)