Genome-Scale Imaging of the 3D Organization and Transcriptional Activity of Chromatin.
Genome-Scale Imaging of the 3D Organization and Transcriptional Activity of Chromatin.
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DOI：
10.1016/j.cell.2020.07.032
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发表时间：
2020-09-17
期刊：
影响因子：
64.5
通讯作者：
Zhuang X
中科院分区：
文献类型：
--
作者：
Su JH;Zheng P;Kinrot SS;Bintu B;Zhuang X
染色质的3D组织调节许多基因组功能。我们对3D基因组组织的理解需要工具来直接可视化染色质构象。在这里，我们报告了一种成像技术，用于在具有高基因组通量的单细胞中跨多个尺度可视化染色质组织。首先，我们展示了通过顺序杂交对数百个基因组位点进行多重成像，这允许对整个染色体进行高分辨率构象追踪。接下来，我们报告了一种基于多路错误鲁棒荧光原位杂交（MERFISH）的方法，用于基因组规模的染色质追踪，并展示了1,000多个基因组位点和1,000多个基因的新生转录本以及地标性核结构的同时成像。使用这种技术，我们的特点染色质结构域，车厢，和跨染色体的相互作用和它们的关系，在单细胞中的转录。我们设想这种高通量、多尺度和多模式成像技术的广泛应用，该技术提供了染色质组织在其天然结构和功能背景下的综合视图。Su等人提出了一种高通量、多模式成像平台，用于在数千个细胞中在其功能背景下以基因组规模测定染色质的3D组织。该平台可以集成测量1,000多个基因组位点以及具有里程碑核结构的相同细胞中1,000多个基因的转录活性，从而可以将基因活性与染色体折叠直接联系起来，并回答有趣的生物学问题。
The 3D organization of chromatin regulates many genome functions. Our understanding of 3D genome organization requires tools to directly visualize chromatin conformation in its native context. Here we report an imaging technology for visualizing chromatin organization across multiple scales in single cells with high genomic throughput. First we demonstrate multiplexed imaging of hundreds of genomic loci by sequential hybridization, which allows high-resolution conformation tracing of whole chromosomes. Next we report a multiplexed error-robust fluorescence in situ hybridization (MERFISH)-based method for genome-scale chromatin tracing and demonstrate simultaneous imaging of more than 1,000 genomic loci and nascent transcripts of more than 1,000 genes together with landmark nuclear structures. Using this technology, we characterize chromatin domains, compartments, and trans-chromosomal interactions and their relationship to transcription in single cells. We envision broad application of this high-throughput, multi-scale, and multi-modal imaging technology, which provides an integrated view of chromatin organization in its native structural and functional context. Su et al. present a high-throughput, multi-modal imaging platform to assay the 3D organization of chromatin at genome scale in its functional context in thousands of cells. This platform enables integrated measurements of more than 1,000 genomic loci together with the transcription activity of more than 1,000 genes in the same cells with landmark nuclear structures, making it possible to directly link gene activity to chromosome folding and to answer interesting biological questions.
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