AbstractThe human genome is extensively folded into 3-dimensional organization, yet 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 a novel 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 (5×5×30 nm in xyz dimensions, respectively). We applied 3D-EMISH to human lymphoblastoid cells at a 1.7 Mb segment of the genome and visualized a large number of distinctive 3D chromatin folding structures in high ultra-resolution. We further quantitatively characterized the reconstituted chromatin folding structures by identifying sub-domains, and uncovered a high level of heterogeneity in chromatin folding ultrastructures, suggestive of extensive dynamic fluidity in 3D chromatin states.
Glomerular Cellular Interactions Following Disruption of the Glomerular Basement Membrane in IgA Nephropathy: Ultrastructural Analyses by 3-Dimensional Serial Block-Face Scanning Electron Microscopy
