Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA.
RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA.
J Cell Biol. 2019 May 6;218(5):1467-1477. doi: 10.1083/jcb.201807162. Epub 2019 Mar 7.
In contrast to the well-studied condensation and folding of chromosomes during mitosis, their dynamics during interphase are less understood. We deployed a CRISPR-based DNA imaging system to track the dynamics of genomic loci situated kilobases to megabases apart on a single chromosome. Two distinct modes of dynamics were resolved: local movements as well as ones that might reflect translational movements of the entire domain within the nucleoplasmic space. The magnitude of both of these modes of movements increased from early to late G1, whereas the translational movements were reduced in early S phase. The local fluctuations decreased slightly in early S and more markedly in mid-late S. These newly observed movements and their cell cycle dependence suggest the existence of a hitherto unrecognized compaction-relaxation dynamic of the interphase chromosome fiber, operating concurrently with changes in the extent of overall movements of loci in the 4D genome.
与有丝分裂过程中染色体的良好研究的凝聚和折叠相比，其在间期的动力学尚不清楚。我们部署了基于 CRISPR 的 DNA 成像系统来跟踪位于单个染色体上数千个碱基对到数百万个碱基对的基因组位置的动力学。解决了两种不同的动力学模式：局部运动以及可能反映整个域在核质空间内平移运动的运动。这两种运动模式的幅度从早 G1 增加到晚 G1，而在早 S 期，平移运动减少。局部波动在早 S 期略有下降，在中晚期 S 期更为明显。这些新观察到的运动及其细胞周期依赖性表明，存在一种迄今未被识别的间期染色体纤维的压缩-松弛动态，与 4D 基因组中基因座整体运动程度的变化同时发生。
