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The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension

Authors: Haarhuis, Judith H.I.; van Der Weide, Robin; Blomen, Vincent; Yáñez-Cuna, J. Omar; Amendola, Mario; van Ruiten, Marjon; Krijger, Peter H.L.; +6 Authors

The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension

Abstract

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.

Countries
Italy, France
Keywords

[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, CCCTC-Binding Factor, Chromosomal Proteins, Non-Histone, Fatty Acid Elongases, cohesin, Cell Cycle Proteins, NIPBL, Article, SCC2, SCC4, Acetyltransferases, Proto-Oncogene Proteins, Humans, chromatin looping, TADs, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cohesins, Cell Nucleus, Gene Editing, loop extrusion, Nuclear Proteins, MAU2, CTCF, Chromatin, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, DNA-Binding Proteins, Repressor Proteins, WAPL, Multiprotein Complexes, Carrier Proteins

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    711
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
711
Top 0.1%
Top 1%
Top 0.1%
Green
hybrid