Two independent modes of chromatin organization revealed by cohesin removal

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Schwarzer, W (Author) Other; Abdennur, N (Author) Other; Goloborodko, A (Author) Other; Pekowska, A (Author) Other; Fudenberg, G (Author) Other; Loe Mie, Y (Author) Other; Nuno A Fonseca (Author) Other; Huber, W (Author) Other; Haering, CH (Author) Other; Mirny, L (Author) Other; Spitz, F (Author) Other

Journal

Title: Nature

Vol. 551

Pages: 51-56

ISSN: 0028-0836

Publisher: Springer Nature

Indexing

Scopus - 328 Citations

Other information

Authenticus ID: P-00N-6ZZ

DOI: 10.1038/nature24281

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific