Coupling chromatin structure and dynamics by live super-resolution imaging
Coupling chromatin structure and dynamics by live super-resolution imaging
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通过实时超分辨率成像耦合染色质结构和动力学
DOI：
10.1126/sciadv.aaz2196
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发表时间：
2020-07-01
期刊：
影响因子：
13.6
通讯作者：
Shaban, H. A.
中科院分区：
文献类型：
--
作者：
Barth, R.;Bystricky, K.;Shaban, H. A.
染色质构象调节基因表达，因此，染色质结构的不断重塑对于保证适当的细胞功能至关重要。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得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，我们发现了类似于45至90 nm宽的染色质“斑点”。“一个计算染色质模型表明，这些斑点动态地将染色质片段与紧密的物理和基因组接近度相关联，并在时间平均限制下采用拓扑相关的结构域样相互作用。实验上，我们发现，染色质表现出时空相关超过类似4 μ m的空间和几十秒的时间，而染色质动力学相关超过类似6 μ m和最后40秒。值得注意的是，染色质结构和动力学是密切相关的，这可能构成了一种机制，以授予访问具有高局部染色质浓度的区域。
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 similar to 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 similar to 4 mu m in space and tens of seconds in time, while chromatin dynamics are correlated over similar to 6 mu m 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.