Two independent modes of chromatin organization revealed by cohesin removal
Author(s)Schwarzer, Wibke; Abdennur, Nezar; Goloborodko, Anton; Pekowska, Aleksandra; Fudenberg, Geoffrey; Loe-Mie, Yann; Fonseca, Nuno A; Huber, Wolfgang; Haering, Christian H.; Mirny, Leonid A; Spitz, Francois; ... Show more Show less
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Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes.
DepartmentMassachusetts Institute of Technology. Department of Physics; Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Springer Science and Business Media
Wibke Schwarzer, et al. "Two independent modes of chromatin organization revealed by cohesin removal." Nature 551, 7678 (September 2017): 51–56 © 2017 Macmillan Publishers Limited, part of Springer Nature
Author's final manuscript