Two independent modes of chromatin organization revealed by cohesin removal.

Abstract

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.

Authors

Schwarzer W  •  Abdennur N  •  Goloborodko A  •  Pekowska A  •  Fudenberg G  •  Loe-Mie Y  •  Fonseca NA  •  Huber W  •  H Haering C  •  Mirny L  •  Spitz F

Link

https://www.ncbi.nlm.nih.gov/pubmed/29094699