Single-cell Hi-C reveals cell-to-cell variability in chromosome structure.
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.
Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
Takashi
T
Nagano
Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute, Rehovot, Israel.
Yaniv
Y
Lubling
Department of Biochemistry, University of Cambridge, UK.
Tim J
TJ
Stevens
Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
Stefan
S
Schoenfelder
Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute, Rehovot, Israel.
Eitan
E
Yaffe
Epigenetics Programme, The Babraham Institute, Cambridge, UK.
Wendy
W
Dean
Department of Biochemistry, University of Cambridge, UK.
Ernest D
ED
Laue
Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute, Rehovot, Israel.
Amos
A
Tanay
Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
Peter
P
Fraser
D000818:Animals; D002467:Cell Nucleus / Q000235:genetics; D002843:Chromatin / Q000737:chemistry; D002875:Chromosomes / Q000737:chemistry* / Q000235:genetics; D005821:Genetic Techniques; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D059010:Single-Cell Analysis; D014960:X Chromosome / Q000737:chemistry / Q000235:genetics
D002843:Chromatin