TY - JOUR
T1 - Long-range interactions between topologically associating domains shape the four-dimensional genome during differentiation
AU - Paulsen, Jonas
AU - Liyakat Ali, Tharvesh M.
AU - Nekrasov, Maxim
AU - Delbarre, Erwan
AU - Baudement, Marie Odile
AU - Kurscheid, Sebastian
AU - Tremethick, David
AU - Collas, Philippe
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85064736900&partnerID=8YFLogxK
U2 - 10.1038/s41588-019-0392-0
DO - 10.1038/s41588-019-0392-0
M3 - Article
SN - 1061-4036
VL - 51
SP - 835
EP - 843
JO - Nature Genetics
JF - Nature Genetics
IS - 5
ER -