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通过实时超分辨率成像耦合染色质结构与动力学

Coupling chromatin structure and dynamics by live super-resolution imaging.

作者信息

Barth R, Bystricky K, Shaban H A

机构信息

Laboratoire de Biologie Moléculaire Eucaryote (LBME), Centre de Biologie Intégrative (CBI), CNRS, University of Toulouse, UPS, 31062 Toulouse, France.

Department of Bionanoscience, Delft University of Technology, 2628 CJ, Delft, Netherlands.

出版信息

Sci Adv. 2020 Jul 1;6(27). doi: 10.1126/sciadv.aaz2196. Print 2020 Jul.

Abstract

Chromatin conformation regulates gene expression and thus, constant remodeling of chromatin structure is essential to guarantee proper cell function. To gain insight into the spatiotemporal organization of the genome, we use high-density photoactivated localization microscopy and deep learning to obtain temporally resolved super-resolution images of chromatin in living cells. In combination with high-resolution dense motion reconstruction, we find elongated ~45- to 90-nm-wide chromatin "blobs." A computational chromatin model suggests that these blobs are dynamically associating chromatin fragments in close physical and genomic proximity and adopt topologically associated domain-like interactions in the time-average limit. Experimentally, we found that chromatin exhibits a spatiotemporal correlation over ~4 μm in space and tens of seconds in time, while chromatin dynamics are correlated over ~6 μm and last 40 s. Notably, chromatin structure and dynamics are closely related, which may constitute a mechanism to grant access to regions with high local chromatin concentration.

摘要

染色质构象调节基因表达,因此,染色质结构的持续重塑对于保证细胞正常功能至关重要。为了深入了解基因组的时空组织,我们使用高密度光激活定位显微镜和深度学习来获取活细胞中染色质的时间分辨超分辨率图像。结合高分辨率密集运动重建,我们发现了细长的、宽度约为45至90纳米的染色质“斑点”。一个计算染色质模型表明,这些斑点是在物理和基因组上紧密相邻的动态关联染色质片段,并且在时间平均极限下采用拓扑相关结构域样相互作用。实验上,我们发现染色质在空间上表现出约4微米的时空相关性,在时间上表现出数十秒的相关性,而染色质动力学在约6微米的范围内相关且持续40秒。值得注意的是,染色质结构和动力学密切相关,这可能构成一种机制,使得能够接触到局部染色质浓度高的区域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb8/7458449/96b767f3b3a7/aaz2196-F1.jpg

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