Two independent modes of chromatin organization revealed by cohesin removal

• Main Authors: Schwarzer, Wibke (Author), Abdennur, Nezar (Author), Goloborodko, Anton (Author), Pekowska, Aleksandra (Author), Fudenberg, Geoffrey (Author), Loe-Mie, Yann (Author), Fonseca, Nuno A (Author), Huber, Wolfgang (Author), Haering, Christian H. (Author), Mirny, Leonid A (Author), Spitz, Francois (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Physics (Contributor), Massachusetts Institute of Technology. Institute for Medical Engineering & Science (Contributor)
• Format: Article
• Language: English
• Published: Springer Science and Business Media, 2020-08-05T19:03:33Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institutes of Health (Grant R01-GM114190, U54-DK107980)
National Science Foundation (Grant 1504942)