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Single-cell Hi-C reveals cell-to-cell variability in chromosome structure.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Nagano, Takashi 
Lubling, Yaniv 
Stevens, Tim J 
Schoenfelder, Stefan  ORCID logo  https://orcid.org/0000-0002-3200-8133
Yaffe, Eitan 

Abstract

Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture (3C) assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from millions of nuclei. Here we introduce single-cell Hi-C, combined with genome-wide statistical analysis and structural modelling of single-copy X chromosomes, to show that individual chromosomes maintain domain organization at the megabase scale, but show variable cell-to-cell chromosome structures at larger scales. Despite this structural stochasticity, localization of active gene domains to boundaries of chromosome territories is a hallmark of chromosomal conformation. Single-cell Hi-C data bridge current gaps between genomics and microscopy studies of chromosomes, demonstrating how modular organization underlies dynamic chromosome structure, and how this structure is probabilistically linked with genome activity patterns.

Description

Keywords

Animals, Cell Nucleus, Chromatin, Chromosomes, Genetic Techniques, Male, Mice, Models, Molecular, Molecular Conformation, Single-Cell Analysis, X Chromosome

Journal Title

Nature

Conference Name

Journal ISSN

0028-0836
1476-4687

Volume Title

502

Publisher

Springer Nature

Rights

All rights reserved
Sponsorship
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0404)