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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.
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Submitted on : Thursday, June 18, 2020 - 12:27:43 PM
Last modification on : Friday, May 6, 2022 - 2:54:41 PM

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Wibke Schwarzer, Nezar Abdennur, Anton Goloborodko, Aleksandra Pekowska, Geoffrey Fudenberg, et al.. Two independent modes of chromatin organization revealed by cohesin removal. Nature, Nature Publishing Group, 2017, 551 (7678), pp.51-56. ⟨10.1038/nature24281⟩. ⟨pasteur-02873504⟩



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