Cohesin loss eliminates all loop domains

By Suhas S. P. Rao, Su-Chen Huang, B. G. S. Hilaire, J. Engreitz, Elizabeth M. Perez, Kyong-Rim Kieffer-Kwon, Adrian L. Sanborn, Sarah E. Johnstone, Gavin D. Bascom, Ivan D. Bochkov and 12 more. Cell, 2017

1,648 citations recorded by the source corpus.

SUMMARY The human genome folds to create thousands of intervals, called “contact domains,” that exhibit enhanced contact frequency within themselves. “Loop domains” form because of tethering between two loci – almost always bound by CTCF and cohesin – lying on the same chromosome. “Compartment domains” form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation, but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes, and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation of each loop. Although reformation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/45bcad8c7fa58b22fa0f17655bcee52b1f47a10a

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Citations in the corpus

Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells (2018, background): “The loop extrusion model (22, 40), in which cohesin complexes extrude DNA until stopped by a pair of CTCF motifs, has been proposed to explain the formation of TADs and sub-TADs at the population level (22, 25, 40, 41).”
Juicebox.js Provides a Cloud-Based Visualization System for Hi-C Data (2017, positive): “For a recent publication, we used Juicebox.js to create five interactive figures, which the journal was able to host alongside the online version of the paper (Rao et al., 2017) (see Table S1.)”
Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins (2017, neutral): “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).”
Organization of Chromatin by Intrinsic and Regulated Phase Separation (2019, background): “topologically associated domains), constrained in a cohesindependent manner (Bintu et al., 2018; Lieberman-Aiden et al., 2009; Rao et al., 2017), enriched in particular post-translational modifications and chromatin-binding proteins.”
Gene-specific H1 eviction through a transcriptional activator-p300-NAP1-H1 pathway (2019, result): “The results also are consistent with recent reports that CTCF degradation has minimal immediate effect on transcription (Rao et al., 2017; Zuin et al., 2014) and that H1 loss can have significant effects on chromosome organization without major transcriptional changes (Geeven et al.”
Coactivator condensation at super-enhancers links phase separation and gene control (2018, background): “Cohesin, an SMC (structural maintenance of chromosomes) protein complex, has been implicated in constraining SE-SE interactions because its loss causes extensive fusion of SEswithin the nucleus (56).”
Targeted Protein Depletion Using the Auxin‐Inducible Degron 2 (AID2) System (2021, methodology): “Since then, the original AID system has been used in many studies for observing immediate consequences after rapid depletion of proteins of interest in this system (Gibcus et al., 2018; Nora et al., 2017; Rao et al., 2017; Sybirna et al., 2020).”