The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension

By Judith H. I. Haarhuis, Robin H. van der Weide, V. Blomen, J. Yáñez-Cuna, Mario Amendola, M. S. van Ruiten, Peter H. L. Krijger, Hans Teunissen, R. Medema, B. van Steensel and 3 more. Cell, 2017

699 citations recorded by the source corpus.

Summary The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin’s DNA release factor WAPL restricts this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ccf9ed3bd806d283989c2c5795aebea3f20dbe1e

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Citations in the corpus

Cohesin loss eliminates all loop domains (2017, background): “Similarly, deletion of WAPL appears to increase the processivity of the Xcom, and thus increases the size of loops (Haarhuis et al., 2017).”
Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins (2017, positive): “In these studies, chromatin structure was analyzed by Hi-C experiments following inactivation of either cohesin (Rao et al, 2017), the cohesin loading complex (Schwarzer et al, 2017), CTCF (Nora et al, 2017), or WAPL (Haarhuis et al, 2017).”
Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells (2018, background): “It has been suggested that the collision between two loop extruders could facilitate three-way chromatin interactions (26, 43, 44).”