Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization.
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
07 03 2019
07 03 2019
Historique:
received:
09
11
2017
revised:
18
10
2018
accepted:
09
01
2019
pmc-release:
07
03
2020
pubmed:
26
2
2019
medline:
7
1
2020
entrez:
26
2
2019
Statut:
ppublish
Résumé
Several general principles of global 3D genome organization have recently been established, including non-random positioning of chromosomes and genes in the cell nucleus, distinct chromatin compartments, and topologically associating domains (TADs). However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are still poorly characterized. Here, we systematically probe heterogeneity in genome organization. High-throughput optical mapping of several hundred intra-chromosomal interactions in individual human fibroblasts demonstrates low association frequencies, which are determined by genomic distance, higher-order chromatin architecture, and chromatin environment. The structure of TADs is variable between individual cells, and inter-TAD associations are common. Furthermore, single-cell analysis reveals independent behavior of individual alleles in single nuclei. Our observations reveal extensive variability and heterogeneity in genome organization at the level of individual alleles and demonstrate the coexistence of a broad spectrum of genome configurations in a cell population.
Identifiants
pubmed: 30799036
pii: S0092-8674(19)30053-4
doi: 10.1016/j.cell.2019.01.020
pmc: PMC6408223
mid: NIHMS1518663
pii:
doi:
Substances chimiques
Chromatin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1502-1515.e10Subventions
Organisme : NIDDK NIH HHS
ID : U54 DK107980
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC010309-20
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Published by Elsevier Inc.
Références
Genome Res. 2016 Jan;26(1):70-84
pubmed: 26518482
Science. 2013 Aug 9;341(6146):660-4
pubmed: 23929981
Nat Commun. 2017 Nov 24;8(1):1753
pubmed: 29170434
Nature. 2017 Apr 6;544(7648):110-114
pubmed: 28355183
Nature. 2014 Dec 18;516(7531):432-435
pubmed: 25307058
Nucleus. 2018 Jan 1;9(1):20-32
pubmed: 29077530
Nucleic Acids Res. 2010 Nov;38(21):7472-84
pubmed: 20660483
Microbiol Mol Biol Rev. 2015 Sep;79(3):347-72
pubmed: 26223848
Curr Biol. 2002 Mar 19;12(6):439-45
pubmed: 11909528
Science. 2009 Oct 9;326(5950):289-93
pubmed: 19815776
Nat Methods. 2017 Jul;14(7):673-678
pubmed: 28604723
Nature. 2017 Sep 13;549(7671):219-226
pubmed: 28905911
Mol Cell. 2018 Apr 19;70(2):287-296.e6
pubmed: 29606591
Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4504-12
pubmed: 27432957
Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):E1663-72
pubmed: 26951677
Cell. 2014 Dec 18;159(7):1665-80
pubmed: 25497547
Mol Cell Biol. 2004 Apr;24(7):2842-52
pubmed: 15024073
Nature. 2017 Apr 6;544(7648):59-64
pubmed: 28289288
Science. 2017 Jul 28;357(6349):
pubmed: 28751582
Science. 2018 Aug 31;361(6405):924-928
pubmed: 30166492
Nature. 2017 Mar 23;543(7646):519-524
pubmed: 28273065
Cell Rep. 2016 May 31;15(9):2038-49
pubmed: 27210764
PLoS Comput Biol. 2016 Dec 27;12(12):e1005292
pubmed: 28027298
Bioinformatics. 2016 Jun 1;32(11):1601-9
pubmed: 26315910
EMBO J. 2017 Dec 15;36(24):3600-3618
pubmed: 29217590
Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):E6456-65
pubmed: 26499245
Nat Genet. 2018 Sep;50(9):1296-1303
pubmed: 30038397
Nature. 2017 Jul 5;547(7661):61-67
pubmed: 28682332
J Cell Biol. 1998 Apr 6;141(1):5-20
pubmed: 9531544
EMBO J. 2017 Dec 15;36(24):3573-3599
pubmed: 29217591
Cell. 2017 May 4;169(4):693-707.e14
pubmed: 28475897
Epigenetics Chromatin. 2014 Apr 28;7:8
pubmed: 25057298
Science. 2016 Aug 5;353(6299):598-602
pubmed: 27445307
Nature. 2013 Nov 14;503(7475):290-4
pubmed: 24141950
Chromosoma. 2017 Feb;126(1):33-44
pubmed: 27130552
Cell. 2017 May 18;169(5):930-944.e22
pubmed: 28525758
Stat Appl Genet Mol Biol. 2016 Dec 1;15(6):447-471
pubmed: 27875323
Genome Biol. 2010;11(2):R22
pubmed: 20181287
Cold Spring Harb Symp Quant Biol. 2017;82:45-55
pubmed: 29728444
Development. 2007 Mar;134(5):909-19
pubmed: 17251268
Science. 2004 Nov 26;306(5701):1574-7
pubmed: 15567868
Nature. 2012 Sep 6;489(7414):57-74
pubmed: 22955616
Nature. 2012 Apr 11;485(7398):381-5
pubmed: 22495304
Sci Adv. 2018 Feb 28;4(2):eaar8082
pubmed: 29503869
Annu Rev Genomics Hum Genet. 2013;14:67-84
pubmed: 23875797
Nat Rev Genet. 2013 Aug;14(8):572-84
pubmed: 23835438
Nat Biotechnol. 2011 Dec 25;30(1):90-8
pubmed: 22198700
Cell. 2014 Jul 17;158(2):339-352
pubmed: 24998931
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Nature. 2016 Dec 8;540(7632):296-300
pubmed: 27919068
Methods. 2017 Jul 1;123:47-55
pubmed: 28179124
Cell. 2014 May 8;157(4):950-63
pubmed: 24813616
Cell. 2014 Feb 27;156(5):907-19
pubmed: 24581492
Cold Spring Harb Symp Quant Biol. 2015;80:73-81
pubmed: 26472748
FEBS Lett. 2015 Oct 7;589(20 Pt A):3031-6
pubmed: 26364723
Genome Biol. 2015 May 27;16:110
pubmed: 26013771
Genome Biol. 2015 Aug 03;16:146
pubmed: 26313373
Nat Methods. 2017 Mar;14(3):263-266
pubmed: 28135255
Nature. 2013 Oct 3;502(7469):59-64
pubmed: 24067610
Nature. 2012 Apr 11;485(7398):376-80
pubmed: 22495300
Methods. 2015 Jan 15;72:65-75
pubmed: 25448293
Cell. 2015 Mar 12;160(6):1145-58
pubmed: 25768910
Curr Biol. 1997 Dec 1;7(12):930-9
pubmed: 9382846
Genome Biol. 2016 Oct 19;17(1):215
pubmed: 27760553
Cell. 2015 Aug 13;162(4):911-23
pubmed: 26276637
J Cell Biol. 1999 Oct 4;147(1):13-24
pubmed: 10508851
Cell. 2007 Feb 23;128(4):787-800
pubmed: 17320514
Nucleus. 2013 Sep-Oct;4(5):390-8
pubmed: 24051548
Nature. 2017 Nov 2;551(7678):51-56
pubmed: 29094699
Nat Methods. 2012 Oct;9(10):999-1003
pubmed: 22941365
Nature. 2015 Feb 19;518(7539):331-6
pubmed: 25693564
Mol Syst Biol. 2015 Dec 23;11(12):852
pubmed: 26700852
Nature. 2016 Jan 21;529(7586):418-22
pubmed: 26760202
Science. 2013 Nov 22;342(6161):948-53
pubmed: 24200812
Nucleic Acids Res. 2014 Mar;42(5):2848-55
pubmed: 24366878
BMC Genomics. 2015 Feb 25;16:121
pubmed: 25887659
Cell. 2012 Feb 3;148(3):458-72
pubmed: 22265598