期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-020-15987-2
关键词
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资金
- Human Frontier Science Program [RGP0039/2017]
- NIH [HG009409, DK107967]
- HFSP [RGP0039/2017]
- Roux family endowment
- Polish National Science Center [UMO-2013/08/M/NZ3/00655, 2014/15/N/NZ2/00379, 2017/24/T/NZ2/00307, 2014/15/B/ST6/05082]
- 4DN [U54 DK107967]
- ENCODE consortia [UM1 HG009409]
- Foundation for Polish Science - European Union under the European Regional Development Fund (TEAM)
- ETIUDA grant from Polish National Science Centre [UMO-2019/32/T/NZ4/00502]
- Sonata bis grant from Polish National Science Centre [UMO-2015/18/E/NZ3/00730]
The human genome is extensively folded into 3-dimensional organization. However, the detailed 3D chromatin folding structures have not been fully visualized due to the lack of robust and ultra-resolution imaging capability. Here, we report the development of an electron microscopy method that combines serial block-face scanning electron microscopy with in situ hybridization (3D-EMISH) to visualize 3D chromatin folding at targeted genomic regions with ultra-resolution (5 x 5 x 30nm in xyz dimensions) that is superior to the current super-resolution by fluorescence light microscopy. We apply 3D-EMISH to human lymphoblastoid cells at a 1.7Mb segment of the genome and visualize a large number of distinctive 3D chromatin folding structures in ultra-resolution. We further quantitatively characterize the reconstituted chromatin folding structures by identifying sub-domains, and uncover a high level heterogeneity of chromatin folding ultrastructures in individual nuclei, suggestive of extensive dynamic fluidity in 3D chromatin states. The genome is folded in 3-dimensions, though the lack of robust ultra-resolution imaging makes this difficult to visualise. Here, the authors present 3D-EMISH that combines serial block-face scanning electron microscopy with in situ hybridization.
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