Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Trends Genet. 2020 Apr;36(4):273-287. doi: 10.1016/j.tig.2019.12.010. Epub 2020 Jan 29.
It is now widely appreciated that the spatial organization of the genome is nonrandom, and its complex 3D folding has important consequences for many genome processes. Recent developments in multiplexed, super-resolution microscopy have enabled an unprecedented view of the polymeric structure of chromatin - from the loose folds of whole chromosomes to the detailed loops of cis-regulatory elements that regulate gene expression. Facilitated by the use of robotics, microfluidics, and improved approaches to super-resolution, thousands to hundreds of thousands of individual cells can now be analyzed in an individual experiment. This has led to new insights into the nature of genomic structural features identified by sequencing, such as topologically associated domains (TADs), and the nature of enhancer-promoter interactions underlying transcriptional regulation. We review these recent improvements.
现在人们普遍认识到，基因组的空间组织不是随机的，其复杂的 3D 折叠对许多基因组过程都有重要影响。多重、超分辨率显微镜技术的最新发展使人们能够以前所未有的视角观察染色质的聚合结构——从整个染色体的松散折叠到调节基因表达的顺式调控元件的详细环。通过使用机器人技术、微流控技术和改进的超分辨率方法，可以在单个实验中分析数千到数十万个体细胞。这使得人们对测序确定的基因组结构特征的本质有了新的认识，例如拓扑相关结构域（TAD），以及转录调控背后的增强子-启动子相互作用的本质。我们将对这些最新进展进行综述。
