Two independent modes of chromatin organization are revealed by cohesin removal
Wibke Schwarzer*, Nezar Abdennur*, Anton Goloborodko*, Aleksandra Pekowska, Geoffrey Fudenberg, Yann Loe-Mie, Nuno A Fonseca, Wolfgang Huber, Christian H. Haering, Leonid Mirny & Francois Spitz.
Nature 551, 51–56. doi:10.1038/nature24281
bioRxiv (Dec, 2016) doi:10.1101/094185
Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-large active and inactive compartments, and partitioning into sub-megabase domains (TADs). Yet, it remains unclear how these layers of organization form, interact with one another and impact genome functions. Here, we show that deletion of the cohesin-loading factor Nipbl, in mouse liver, leads to a dramatic reorganization of chromosomal folding. TADs and associated peaks vanish globally, even in the absence of transcriptional changes. In 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 3D organization of the genome results from the interplay of two independent mechanisms: 1) cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; 2) cohesin-dependent formation of TADs, possibly by loop extrusion, which contributes to guide distant enhancers to their target genes.
Highlights and Press
- Nature News and Views by Rachel Patton McCord: Chromosome biology: How to build a cohesive genome in 3D
- Nature Reviews Genetics Highlight by Katharine H. Wrighton: Compartmentalizing chromatin without cohesin
- MIT News by Helen Knight: Researchers identify molecular motor that transforms chromosomes
- Awesomely alliterative highlight at Epigenie: The Hi’s and Lo’s of Cohesin’s Crafty Chromatin Concerto