Microscopy and genomic approaches provide detailed descriptions of the three-dimensional folding of chromosomes and nuclear organization. The fundamental question is how activity of molecules at the nanometer scale can lead to complex and orchestrated spatial organization at the scale of chromosomes and the whole nucleus. At least three key mechanisms can bridge across scales: (1) tethering of specific loci to nuclear landmarks leads to massive reorganization of the nucleus; (2) spatial compartmentalization of chromatin, which is driven by molecular affinities, results in spatial isolation of active and inactive chromatin; and (3) loop extrusion activity of SMC (structural maintenance of chromosome) complexes can explain many features of interphase chromatin folding and underlies key phenomena during mitosis. Interestingly, many features of chromosome organization ultimately result from collective action and the interplay between these mechanisms, and are further modulated by transcription and topological constraints. Finally, we highlight some outstanding questions that are critical for our understanding of nuclear organization and function. We believe many of these questions can be answered in the coming years.

中文翻译：

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染色体折叠和核组织的机制：它们的相互作用和悬而未决的问题


显微镜和基因组方法提供了染色体三维折叠和核组织的详细描述。根本问题是纳米尺度分子的活动如何导致染色体和整个细胞核尺度上复杂且精心策划的空间组织。至少三个关键机制可以跨越尺度：（1）特定位点与核标志物的束缚导致细胞核的大规模重组； (2)由分子亲和力驱动的染色质空间区室化导致活性和非活性染色质的空间隔离； (3) SMC（染色体结构维持）复合物的环挤压活性可以解释间期染色质折叠的许多特征，并且是有丝分裂过程中关键现象的基础。有趣的是，染色体组织的许多特征最终来自集体行动和这些机制之间的相互作用，并进一步受到转录和拓扑约束的调节。最后，我们强调了一些对于我们理解核组织和功能至关重要的悬而未决的问题。我们相信其中许多问题可以在未来几年得到解答。