| First Author | Schwarzer W | Year | 2017 |
| Journal | Nature | Volume | 551 |
| Issue | 7678 | Pages | 51-56 |
| PubMed ID | 29094699 | Mgi Jnum | J:250426 |
| Mgi Id | MGI:6102971 | Doi | 10.1038/nature24281 |
| Citation | Schwarzer W, et al. (2017) Two independent modes of chromatin organization revealed by cohesin removal. Nature 551(7678):51-56 |
| abstractText | 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. |
