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Nat Genet. 2019 May;51(5):835-843. doi: 10.1038/s41588-019-0392-0. Epub 2019 Apr 22.

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

Author information

1
Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
2
Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
3
Biomolecular Research Facility, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
4
Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia. david.tremethick@anu.edu.au.
5
Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway. philc@medisin.uio.no.
6
Norwegian Center for Stem Cell Research, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway. philc@medisin.uio.no.

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.

PMID:
31011212
DOI:
10.1038/s41588-019-0392-0
[Indexed for MEDLINE]

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