Ultrastructural Details of Mammalian Chromosome Architecture
Department of Biochemistry and Molecular Pharmacology; Program in Systems Biology; Program in Molecular Medicine; Diabetes Center of Excellence
Biochemistry, Biophysics, and Structural Biology | Bioinformatics | Cell and Developmental Biology | Systems Biology
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.
CTCF, Chromatin, Chromosomes, Loop extrusion, Micro-C
DOI of Published Version
Krietenstein N, Abraham S, Venev SV, Abdennur N, Gibcus J, Hsieh TS, Parsi KM, Yang L, Maehr R, Mirny LA, Dekker J, Rando OJ. Ultrastructural Details of Mammalian Chromosome Architecture. Mol Cell. 2020 Mar 14:S1097-2765(20)30151-9. doi: 10.1016/j.molcel.2020.03.003. Epub ahead of print. PMID: 32213324. Link to article on publisher's site
Krietenstein N, Abraham S, Venev SV, Abdennur N, Gibcus JH, Hsieh TS, Parsi KM, Yang L, Maehr R, Mirny LA, Dekker J, Rando OJ. (2020). Ultrastructural Details of Mammalian Chromosome Architecture. Program in Systems Biology Publications. https://doi.org/10.1016/j.molcel.2020.03.003. Retrieved from https://escholarship.umassmed.edu/sysbio_pubs/166