Two independent modes of chromatin organization revealed by cohesin removal

By Wibke Schwarzer, Nezar Abdennur, Anton Goloborodko, Aleksandra Pękowska, Geoffrey Fudenberg, Yann Loe-Mie, Nuno A. Fonseca, Wolfgang Huber, C. Haering, Leonid A. Mirny and 1 more. Nature, 2017

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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.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/487c5b10e241b6525db95d73f14e7a8d54de9167

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Citations in the corpus

A pathway for mitotic chromosome formation (2018, background): “Hi-C analysis revealed that in the absence of SMC2, interphase compartments and TADs were still present and largely unaffected by late prophase, at a time when they were completely dis- assembled in the wild type (t = 10 min) (Fig.”
Galaxy HiCExplorer 3: a web server for reproducible Hi-C, capture Hi-C and single-cell Hi-C data analysis, quality control and visualization (2020, methodology): “Hi-C technology is a well established method to study genome wide interaction of data and can detect largescale chromosome structures, such as active and inactive (A/B) compartments (5,6), topological associated domains (TADs) (7,8), chromatin loop structures (9) or ratios of short to long range int”
Chromatin organization by an interplay of loop extrusion and compartmental segregation (2017, background): “Finally, recent experiments directly showed that TADs compete with compartments: Removal or depletion of chromatin-associated cohesin (11–14), which is required for TADs, not only made TADs disappear but also increased compartmentalization (11, 12, 14), sharpened compartment transitions (13), and fr”
Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins (2017, positive): “Our results are, however, consistent with several other studies which were deposited on bioRxiv or published in peer-reviewed journals during preparation or after submission of our manuscript (Gassler et al, 2017; Haarhuis et al, 2017; Nora et al, 2017; Rao et al, 2017; Schwarzer et al, 2017).”
HiGlass: web-based visual exploration and analysis of genome interaction maps (2017, background): “across different conditions, zoom levels, and loci [46].”