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

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

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    84 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)835-843
    Number of pages9
    JournalNature Genetics
    Volume51
    Issue number5
    DOIs
    Publication statusPublished - 1 May 2019

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