Sensitivity of cohesin–chromatin association to high-salt treatment corroborates non-topological mode of loop extrusion

Epigenetics & Chromatin

Anastasia V. Golova¹  Alexey A. Gavrilov²  Sergey V. Razin³  Arkadiy K. Golov⁴ 

[1] Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia;Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia;Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia;Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia;Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia;Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia;Mental Health Research Center, Moscow, Russia;

关键词: Cohesin;    Loop extrusion;    Topological entrapment;    Chromatin folding;    CTCF;   

DOI  :  10.1186/s13072-021-00411-w

来源: Springer

【 摘 要 】

Cohesin is a key organizer of chromatin folding in eukaryotic cells. The two main activities of this ring-shaped protein complex are the maintenance of sister chromatid cohesion and the establishment of long-range DNA–DNA interactions through the process of loop extrusion. Although the basic principles of both cohesion and loop extrusion have been described, we still do not understand several crucial mechanistic details. One of such unresolved issues is the question of whether a cohesin ring topologically embraces DNA string(s) during loop extrusion. Here, we show that cohesin complexes residing on CTCF-occupied genomic sites in mammalian cells do not interact with DNA topologically. We assessed the stability of cohesin-dependent loops and cohesin association with chromatin in high-ionic-strength conditions in G1-synchronized HeLa cells. We found that increased salt concentration completely displaces cohesin from those genomic regions that correspond to CTCF-defined loop anchors. Unsurprisingly, CTCF-anchored cohesin loops also dissipate in these conditions. Because topologically engaged cohesin is considered to be salt resistant, our data corroborate a non-topological model of loop extrusion. We also propose a model of cohesin activity throughout the interphase, which essentially equates the termination of non-topological loop extrusion with topological loading of cohesin. This theoretical framework enables a parsimonious explanation of various seemingly contradictory experimental findings.

【 授权许可】

CC BY