Ultrastructural Details of Mammalian Chromosome Architecture

Nils Krietenstein*, Sameer Abraham, Sergey V. Venev, Nezar Abdennur, Johan Gibcus, Tsung-Han S. Hsieh, Krishna Mohan Parsi, Liyan Yang, René Maehr, Leonid A. Mirny, Job Dekker & Oliver J. Rando

Molecular Cell 78(3), 554-565 doi:10.1016/j.molcel.2020.03.003

bioRxiv (May, 2019) doi:10.1101/639922


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 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.

HiGlass Displays

Comparison of Micro-C (left) v/s Hi-C (right) for H1-hESC cells.
Comparison of Micro-C (left) v/s Hi-C (right) for HFFc6 cells.