Long-range interactions between topologically associating domains shape the four-dimensional genome during differentiation

Date

2019

Authors

Paulsen, Jonas
Ali, Tharvesh M. Liyakat
Nekrasov, Maxim
Delbarre, Erwan
Baudement , Marie-Odile
Kurscheid, Sebastian
Tremethick, David
Collas, Philippe

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Volume Title

Publisher

Nature Publishing Group

Abstract

Genomic information is selectively used to direct spatial and temporal gene expression during differentiation. Interactions between topologically associating domains (TADs) and between chromatin and the nuclear lamina organize and position chromosomes in the nucleus. However, how these genomic organizers together shape genome architecture is unclear. Here, using a dual-lineage differentiation system, we report long-range TAD–TAD interactions that form constitutive and variable TAD cliques. A differentiation-coupled relationship between TAD cliques and lamina-associated domains suggests that TAD cliques stabilize heterochromatin at the nuclear periphery. We also provide evidence of dynamic TAD cliques during mouse embryonic stem-cell differentiation and somatic cell reprogramming and of inter-TAD associations in single-cell high-resolution chromosome conformation capture (Hi-C) data. TAD cliques represent a level of four-dimensional genome conformation that reinforces the silencing of repressed developmental genes.

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Citation

Source

Nature Genetics

Type

Journal article

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DOI

10.1038/s41588-019-0392-0

Restricted until

2037-12-31