Nat Genet. 2019 May;51(5):835-843. doi: 10.1038/s41588-019-0392-0.
Jonas Paulsen, Tharvesh M. Liyakat Ali, Maxim Nekrasov, Erwan Delbarre, Marie-Odile Baudement, Sebastian Kurscheid, David Tremethick and Philippe Collas
A collaboration between the University of Oslo (Collas) and The Australian National University (Tremethick)
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. Using a dual-lineage differentiation system, we report here long-range TAD-TAD interactions forming dynamic 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 Hi-C data. TAD cliques represent a new level of 4-dimensional genome conformation reinforcing the silencing of repressed developmental genes.