Institute for Medical Engineering and Science, and Department of Physics, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA.
Institute for Medical Engineering and Science, and Department of Physics, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA.
Curr Opin Cell Biol. 2019 Jun;58:142-152. doi: 10.1016/j.ceb.2019.05.001. Epub 2019 Jun 20.
The spatial organization of chromosomes has long been connected to their polymeric nature and is believed to be important for their biological functions, including the control of interactions between genomic elements, the maintenance of genetic information, and the compaction and safe transfer of chromosomes to cellular progeny. chromosome conformation capture techniques, particularly Hi-C, have provided a comprehensive picture of spatial chromosome organization and revealed new features and elements of chromosome folding. Furthermore, recent advances in microscopy have made it possible to obtain distance maps for extensive regions of chromosomes (Bintu et al., 2018; Nir et al., 2018 [2,3]), providing information complementary to, and in excellent agreement with, Hi-C maps. Not only has the resolution of both techniques advanced significantly, but new perturbation data generated in the last two years have led to the identification of molecular mechanisms behind large-scale genome organization. Two major mechanisms that have been proposed to govern chromosome organization are (i) the active (ATP-dependent) process of loop extrusion by Structural Maintenance of Chromosomes (SMC) complexes, and (ii) the spatial compartmentalization of the genome, which is likely mediated by affinity interactions between heterochromatic regions (Falk et al., 2019 [76]) rather than by ATP-dependent processes. Here, we review existing evidence that these two processes operate together to fold chromosomes in interphase and that loop extrusion alone drives mitotic compaction. We discuss possible implications of these mechanisms for chromosome function.
染色体的空间组织长期以来与它们的聚合性质相关联，被认为对其生物学功能很重要，包括控制基因组元件之间的相互作用、维持遗传信息、以及将染色体压缩并安全地传递给细胞后代。染色体构象捕获技术，特别是 Hi-C，提供了对空间染色体组织的全面描述，并揭示了新的染色体折叠特征和元件。此外，显微镜技术的最新进展使得获取染色体广泛区域的距离图谱成为可能（Bintu 等人，2018 年；Nir 等人，2018 年[2,3]），为 Hi-C 图谱提供了互补且非常一致的信息。不仅这两种技术的分辨率都有了显著提高，而且在过去两年中产生的新扰动数据导致了对大规模基因组组织背后的分子机制的识别。已经提出了两种主要的机制来控制染色体的组织：（i）结构维持染色体（SMC）复合物的主动（ATP 依赖性）环挤出过程，以及（ii）基因组的空间区隔化，这可能是由异染色质区域之间的亲和相互作用介导的（Falk 等人，2019 年[76]），而不是由 ATP 依赖性过程介导的。在这里，我们回顾了现有的证据，表明这两个过程共同作用以在有丝分裂间期折叠染色体，并且环挤出过程单独驱动有丝分裂的压缩。我们讨论了这些机制对染色体功能的可能影响。
