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New insights into genome folding by loop extrusion from inducible degron technologies.

Elzo de Wit ,
Elphège P Nora

Abstract

Chromatin folds into dynamic loops that often span hundreds of kilobases and physically wire distant loci together for gene regulation. These loops are continuously created, extended and positioned by structural maintenance of chromosomes (SMC) protein complexes, such as condensin and cohesin, and their regulators, including CTCF, in a highly dynamic process known as loop extrusion. Genetic loss of extrusion factors is lethal, complicating their study. Inducible protein degradation technologies enable the depletion of loop extrusion factors within hours, leading to the rapid reconfiguration of chromatin folding. Here, we review how these technologies have changed our understanding of genome organization, upsetting long-held beliefs on its role in transcription. Finally, we examine recent models that attempt to reconcile observations after chronic versus acute perturbations, and discuss future developments in this rapidly developing field of research.

More about this publication

Nature reviews. Genetics

Volume 24
Issue nr. 2
Pages 73-85
Publication date 01-02-2023

Full text links

Publisher website (DOI) 10.1038/s41576-022-00530-4
Europe PubMed Central 36180596
Pubmed 36180596

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