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

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.

journal_name

Nature

journal_title

Nature

authors

Nagano T,Lubling Y,Stevens TJ,Schoenfelder S,Yaffe E,Dean W,Laue ED,Tanay A,Fraser P

doi

10.1038/nature12593

subject

Has Abstract

pub_date

2013-10-03 00:00:00

pages

59-64

issue

7469

eissn

0028-0836

issn

1476-4687

journal_volume

502

pub_type

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