Abstract
Genomic DNA is folded into loops and topologically associating domains (TADs), which serve important structural and regulatory roles. It has been proposed that these genomic structures are formed by a loop extrusion process, which is mediated by structural maintenance of chromosomes (SMC) protein complexes. Recent single-molecule studies have shown that the SMC complexes condensin and cohesin are indeed able to extrude DNA into loops. In this Review, we discuss how the loop extrusion hypothesis can explain key features of genome architecture; cellular functions of loop extrusion, such as separation of replicated DNA molecules, facilitation of enhancer–promoter interactions and immunoglobulin gene recombination; and what is known about the mechanism of loop extrusion and its regulation, for example, by chromatin boundaries that depend on the DNA binding protein CTCF. We also discuss how the loop extrusion hypothesis has led to a paradigm shift in our understanding of both genome architecture and the functions of SMC complexes.
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Acknowledgements
The authors thank M. Busslinger, A. Goloborodko, K. Tachibana and members of the Peters laboratory for helpful discussions. Research in the laboratory of J.-M.P. is supported by Boehringer Ingelheim, the Austrian Research Promotion Agency (Headquarter grant FFG-852936), the European Research Council under the European Union’s Horizon 2020 research and innovation programme GA No. 693949, the Human Frontier Science Program (grant RGP0057/2018) and the Vienna Science and Technology Fund (grant LS19-029). J.-M.P. is also an adjunct professor at the Medical University of Vienna.
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Glossary
- Hi-C
-
A chromatin conformation capture method, in which genomic sequences that are in close proximity inside nuclei are crosslinked to each other, fragmented by restriction enzymes and identified by sequencing, providing information about spatial organization of genomic DNA.
- Micro-C
-
A chromatin conformation capture method that is similar to Hi-C, but involves fragmentation by micrococcal nuclease and provides higher-resolution information about spatial organization of genomic DNA.
- Chromatin interaction analysis with paired-end tags
-
(ChIA-PET). A chromatin conformation capture method, in which genomic sequences that are in close proximity inside nuclei are crosslinked, isolated using antibodies to a chromatin protein of interest and identified by sequencing, providing information about the spatial organization of DNA in regions bound by the protein of interest.
- Type II transposable elements
-
DNA transposons that contain a gene encoding the enzyme transposase, which is an endonuclease that catalyses the excision and insertion of the transposon.
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Davidson, I.F., Peters, JM. Genome folding through loop extrusion by SMC complexes. Nat Rev Mol Cell Biol 22, 445–464 (2021). https://doi.org/10.1038/s41580-021-00349-7
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DOI: https://doi.org/10.1038/s41580-021-00349-7
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