Over the past decade, 3C-related methods have provided remarkable insights into chromosome folding in vivo. To overcome the limited resolution of prior studies, we extend a recently developed Hi-C variant, Micro-C, to map chromosome architecture at nucleosome resolution in human ESCs and fibroblasts. Micro-C robustly captures known features of chromosome folding including compartment organization, topologically associating domains, and interactions between CTCF binding sites. In addition, Micro-C provides a detailed map of nucleosome positions and localizes contact domain boundaries with nucleosomal precision. Compared to Hi-C, Micro-C exhibits an order of magnitude greater dynamic range, allowing the identification of approximately 20,000 additional loops in each cell type. Many newly identified peaks are localized along extrusion stripes and form transitive grids, consistent with their anchors being pause sites impeding cohesin-dependent loop extrusion. Our analyses comprise the highest-resolution maps of chromosome folding in human cells to date, providing a valuable resource for studies of chromosome organization.
Krietenstein N • Abraham S • Venev SV • Abdennur N • Gibcus J • Hsieh TS • Parsi KM • Yang L • Maehr R • Mirny LA • Dekker J • Rando OJ
May 7th, 2020
The Micro-C and Hi-C datasets produced in this publication comprise some of the deepest Hi-C datasets on the 4DN portal (in terms of read depth). The HFFc6 Micro-C experiment set 4DNESWST3UBH is the deepest of all the 4DN data, with 5.86 billion read pairs.
Micro-C maps of H1 hESCs and HFFs tend to look very similar at mid-level resolutions, but at higher resolutions, close to nucleosome-level, Micro-C has a much higher signal-to-noise ratio. Below are comparisons of Micro-C and Hi-C in both cell types, first at 5kb resolution and below that at 50kb resolution.