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Investigating genome plasticity at the nanoscale.
Farabella I., Nir G., Lee S.D., Marti-Renom M.A., Wu C.-T.
Recent advances in image-based 3D genomics techniques have enabled single-cell omics analysis in a spatially resolved manner in intact cells. One such approach is sequential-OligoSTORM (seq-OligoSTORM), which couples the use of Oligopaints probes to achieve super-resolution via single-molecule localisation microscopy. Coupling seq-OligoSTORM with our suite of modelling and analysis tools, we visualised and quantified structures ranging in size from tens of kilobases to over one megabase, detailing the variation in chromatin arrangement at the nanoscale in single nuclei. Focusing on chromosomal regions at the megabase scale, we identified chromatin arrangements that can predict whether regions correspond to active (A-type) or inactive (B-type) compartments. This outcome suggests that variation in patterns of chromatin folding may ultimately reflect specific signatures.