Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
Nat Rev Mol Cell Biol. 2021 Jul;22(7):445-464. doi: 10.1038/s41580-021-00349-7. Epub 2021 Mar 25.
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.
基因组 DNA 折叠成环和拓扑关联域（TADs），它们具有重要的结构和调节作用。有人提出，这些基因组结构是通过环挤出过程形成的，该过程由染色体结构维持（SMC）蛋白复合物介导。最近的单分子研究表明，SMC 复合物 condensin 和 cohesin 确实能够将 DNA 挤出成环。在这篇综述中，我们讨论了环挤出假说如何解释基因组结构的关键特征；环挤出的细胞功能，例如复制 DNA 分子的分离、促进增强子-启动子相互作用和免疫球蛋白基因重组；以及关于环挤出机制及其调控的已知信息，例如，依赖于 DNA 结合蛋白 CTCF 的染色质边界。我们还讨论了环挤出假说如何导致我们对基因组结构和 SMC 复合物功能的理解发生范式转变。
