Developmental differences in genome replication program and origin activation.
Animals
Cell Differentiation
/ genetics
Centromere
/ genetics
Chromosome Duplication
/ genetics
Chromosomes, Human, Y
/ genetics
DNA Replication
/ genetics
Genome
/ genetics
Heterochromatin
/ genetics
Humans
Mice
Mouse Embryonic Stem Cells
/ cytology
Pluripotent Stem Cells
/ cytology
S Phase
/ genetics
Single Molecule Imaging
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
16 12 2020
16 12 2020
Historique:
accepted:
04
11
2020
revised:
09
10
2020
received:
30
06
2020
pubmed:
3
12
2020
medline:
15
1
2021
entrez:
2
12
2020
Statut:
ppublish
Résumé
To ensure error-free duplication of all (epi)genetic information once per cell cycle, DNA replication follows a cell type and developmental stage specific spatio-temporal program. Here, we analyze the spatio-temporal DNA replication progression in (un)differentiated mouse embryonic stem (mES) cells. Whereas telomeres replicate throughout S-phase, we observe mid S-phase replication of (peri)centromeric heterochromatin in mES cells, which switches to late S-phase replication upon differentiation. This replication timing reversal correlates with and depends on an increase in condensation and a decrease in acetylation of chromatin. We further find synchronous duplication of the Y chromosome, marking the end of S-phase, irrespectively of the pluripotency state. Using a combination of single-molecule and super-resolution microscopy, we measure molecular properties of the mES cell replicon, the number of replication foci active in parallel and their spatial clustering. We conclude that each replication nanofocus in mES cells corresponds to an individual replicon, with up to one quarter representing unidirectional forks. Furthermore, with molecular combing and genome-wide origin mapping analyses, we find that mES cells activate twice as many origins spaced at half the distance than somatic cells. Altogether, our results highlight fundamental developmental differences on progression of genome replication and origin activation in pluripotent cells.
Identifiants
pubmed: 33264404
pii: 6017362
doi: 10.1093/nar/gkaa1124
pmc: PMC7736824
doi:
Substances chimiques
Heterochromatin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12751-12777Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Dev Biol. 1967 Nov;16(5):457-73
pubmed: 6053288
Cell. 1988 Aug 12;54(4):505-13
pubmed: 3042152
Nucleic Acids Res. 2011 May;39(9):3594-606
pubmed: 21252296
Curr Biol. 2010 Dec 7;20(23):2067-77
pubmed: 21074439
Annu Rev Cell Dev Biol. 2013;29:241-70
pubmed: 23834025
Mol Cell. 2017 Jul 20;67(2):282-293.e7
pubmed: 28712725
Histochem Cell Biol. 2006 Jan;125(1-2):91-102
pubmed: 16231189
Nucleic Acids Res. 2005 Jan 13;33(1):325-36
pubmed: 15653633
Exp Cell Res. 1996 Aug 1;226(2):328-35
pubmed: 8806436
Dev Biol. 1996 Dec 15;180(2):618-30
pubmed: 8954732
Cell Cycle. 2005 Jan;4(1):172-6
pubmed: 15611667
Cell Syst. 2018 Nov 28;7(5):482-495.e10
pubmed: 30414923
Curr Opin Genet Dev. 2006 Oct;16(5):490-5
pubmed: 16904310
PLoS One. 2012;7(10):e47848
pubmed: 23112857
Chromosoma. 1992 Mar;101(5-6):322-32
pubmed: 1374304
Nat Rev Mol Cell Biol. 2019 Dec;20(12):721-737
pubmed: 31477886
J Cell Sci. 1995 Aug;108 ( Pt 8):2801-9
pubmed: 7593321
Cell. 2009 Apr 17;137(2):356-68
pubmed: 19379699
Nat Commun. 2016 Apr 07;7:11207
pubmed: 27052359
Cell. 1992 Jun 12;69(6):915-26
pubmed: 1606615
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12550-5
pubmed: 22802651
PLoS Genet. 2014 May 01;10(5):e1004282
pubmed: 24785686
Development. 2016 Dec 1;143(23):4301-4311
pubmed: 27899507
Cytometry. 1997 Nov 1;29(3):261-6
pubmed: 9389443
Nat Commun. 2018 Apr 23;9(1):1590
pubmed: 29686321
J Cell Biol. 2001 Apr 2;153(1):101-10
pubmed: 11285277
Genes Dev. 2015 Mar 1;29(5):555-66
pubmed: 25737283
Brief Funct Genomics. 2016 Jul;15(4):305-14
pubmed: 26206085
BMC Cell Biol. 2005 Dec 07;6:44
pubmed: 16336643
J Cell Biol. 2001 Jan 8;152(1):15-25
pubmed: 11149917
J Biomed Biotechnol. 2001;1(1):18-24
pubmed: 12488622
J Cell Sci. 1994 Aug;107 ( Pt 8):2191-202
pubmed: 7983177
Genome Biol. 2015 Aug 10;16:154
pubmed: 26257189
Nat Rev Genet. 2007 Aug;8(8):588-600
pubmed: 17621316
Dev Cell. 2004 Jan;6(1):117-31
pubmed: 14723852
Nature. 2003 Jun 19;423(6942):825-37
pubmed: 12815422
Methods Mol Biol. 2019;2038:199-208
pubmed: 31407286
Cell. 1982 Oct;30(3):675-86
pubmed: 6183003
Nat Commun. 2016 Apr 07;7:11231
pubmed: 27052570
PLoS Biol. 2008 Oct 7;6(10):e245
pubmed: 18842067
Genome Res. 2015 Aug;25(8):1091-103
pubmed: 26055160
Nat Methods. 2019 Dec;16(12):1226-1232
pubmed: 31570887
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15837-42
pubmed: 18838675
Nat Genet. 2002 Nov;32(3):438-42
pubmed: 12355067
Nature. 1977 Dec 22-29;270(5639):725-7
pubmed: 563524
PeerJ. 2014 Jun 19;2:e453
pubmed: 25024921
Nucleic Acids Res. 2012 Jan;40(1):159-69
pubmed: 21908399
J Cell Biol. 2004 Aug 16;166(4):493-505
pubmed: 15302854
Mol Cell. 2002 Dec;10(6):1453-65
pubmed: 12504019
PLoS One. 2013 Dec 10;8(12):e81156
pubmed: 24339907
Nat Rev Genet. 2003 Aug;4(8):598-612
pubmed: 12897772
Genes Cells. 2007 Apr;12(4):447-60
pubmed: 17397393
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
J Cell Biol. 2005 Jun 6;169(5):733-43
pubmed: 15939760
Nucleus. 2020 Dec;11(1):66-82
pubmed: 32275847
Crit Rev Biochem Mol Biol. 2017 Apr;52(2):107-144
pubmed: 28094588
Science. 1995 Nov 10;270(5238):994-7
pubmed: 7481806
Methods Mol Biol. 2015;1300:67-78
pubmed: 25916705
Cold Spring Harb Symp Quant Biol. 1974;38:205-23
pubmed: 4208784
Nature. 2008 Sep 25;455(7212):557-60
pubmed: 18716622
Nature. 2009 Aug 13;460(7257):863-8
pubmed: 19587682
J Cell Biol. 1989 Jan;108(1):1-11
pubmed: 2910875
J Cell Sci. 1989 Nov;94 ( Pt 3):471-7
pubmed: 2632579
Curr Opin Cell Biol. 2016 Jun;40:47-59
pubmed: 26938331
Nucleus. 2019 Dec;10(1):231-253
pubmed: 31744372
Genes Dev. 2000 Apr 15;14(8):940-50
pubmed: 10783166
Protoplasma. 2017 May;254(3):1151-1162
pubmed: 27943022
Genes Dev. 2008 May 15;22(10):1319-24
pubmed: 18443145
Methods Mol Biol. 2015;1300:43-65
pubmed: 25916704
Cell. 2013 Jun 6;153(6):1281-95
pubmed: 23706625
Cytometry. 1989 Mar;10(2):143-50
pubmed: 2469556
Nat Commun. 2017 Jun 12;8:15760
pubmed: 28604675
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):139-44
pubmed: 19966280
EMBO J. 1993 Dec;12(12):4511-20
pubmed: 8223461
J Mol Biol. 1968 Mar 14;32(2):327-41
pubmed: 5689363
Nucleic Acids Res. 2012 Dec;40(22):e176
pubmed: 22923521
Nat Rev Mol Cell Biol. 2006 Jul;7(7):540-6
pubmed: 16723974
Cell. 2018 Aug 23;174(5):1127-1142.e19
pubmed: 30078706
Science. 1997 Feb 14;275(5302):993-5
pubmed: 9020085
Genes Cells. 1997 Nov;2(11):667-78
pubmed: 9491801
Cell. 2001 Nov 2;107(3):323-37
pubmed: 11701123
Cell Stem Cell. 2008 May 8;2(5):437-47
pubmed: 18462694
Bioessays. 2003 Feb;25(2):116-25
pubmed: 12539237
Nature. 1987 Dec 10-16;330(6148):576-8
pubmed: 3683574
Genome Biol. 2007;8(8):R169
pubmed: 17705870
Nat Commun. 2019 Jul 22;10(1):3274
pubmed: 31332171
J Cell Biol. 2000 Apr 17;149(2):271-80
pubmed: 10769021
PLoS Genet. 2010 Apr 22;6(4):e1000920
pubmed: 20421929
Cold Spring Harb Perspect Biol. 2010 Apr;2(4):a000737
pubmed: 20452942
Nucleic Acids Res. 2007;35(16):e107
pubmed: 17704126
Cell Cycle. 2004 Dec;3(12):1645-50
pubmed: 15611653
Epigenetics Chromatin. 2018 Oct 23;11(1):61
pubmed: 30352618
Mol Cell. 2002 Nov;10(5):1223-33
pubmed: 12453428
Database (Oxford). 2016 Jun 23;2016:
pubmed: 27337980
Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3433-7
pubmed: 18305168
J Cell Sci. 1992 Nov;103 ( Pt 3):857-62
pubmed: 1478975
Stem Cell Rev. 2005;1(2):131-8
pubmed: 17142847
Dev Cell. 2006 Jan;10(1):105-16
pubmed: 16399082
Genome Biol. 2003;4(9):226
pubmed: 12952526
J Mol Biol. 2013 Nov 29;425(23):4845-55
pubmed: 23557832
Nucleic Acids Res. 2018 Jul 6;46(12):6112-6128
pubmed: 29750270
Curr Biol. 2003 Jun 17;13(12):1019-28
pubmed: 12814547
Chromosome Res. 2010 Jan;18(1):127-36
pubmed: 20013151
Proc Natl Acad Sci U S A. 1981 Dec;78(12):7634-8
pubmed: 6950406
Nat Commun. 2011;2:222
pubmed: 21364561
Eur J Hum Genet. 2017 Nov;25(11):1181-1188
pubmed: 28853720
Trends Cell Biol. 2002 Sep;12(9):432-8
pubmed: 12220864
Genes Dev. 2010 Dec 15;24(24):2812-22
pubmed: 21159821
Biophys J. 2008 Jun;94(12):4957-70
pubmed: 18326650
Nat Commun. 2016 Jan 11;7:10208
pubmed: 26751768
Nature. 2001 Feb 15;409(6822):860-921
pubmed: 11237011
Mol Cell. 2002 Dec;10(6):1355-65
pubmed: 12504011
Chromosoma. 2000 Mar;108(8):471-84
pubmed: 10794569
Exp Cell Res. 1986 Aug;165(2):291-7
pubmed: 3720850
Genetika. 2010 Sep;46(9):1159-63
pubmed: 21058510
J Cell Biol. 2006 Jul 31;174(3):329-38
pubmed: 16880268
Cytometry. 1998 Feb 1;31(2):100-9
pubmed: 9482279
J Cell Biol. 1998 Mar 23;140(6):1285-95
pubmed: 9508763
J Cell Biol. 1999 Oct 4;147(1):25-32
pubmed: 10508852
Hum Mol Genet. 2004 Jan 15;13(2):191-202
pubmed: 14645202
Mol Cell. 1999 Dec;4(6):983-93
pubmed: 10635323
Curr Opin Genet Dev. 2013 Apr;23(2):191-6
pubmed: 23415810
Nat Rev Mol Cell Biol. 2015 Jun;16(6):360-74
pubmed: 25999062
J Cell Sci. 1997 Apr;110 ( Pt 7):889-97
pubmed: 9133676
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278
Methods. 2012 Jun;57(2):158-64
pubmed: 22796403
Nature. 1982 Jul 1;298(5869):100-2
pubmed: 7088157
Mol Cell Biol. 2004 Jun;24(11):4769-80
pubmed: 15143171
J Cell Biol. 1992 Mar;116(5):1095-110
pubmed: 1740468
Nature. 2015 Feb 19;518(7539):331-6
pubmed: 25693564
Genes Cells. 1997 Nov;2(11):655-65
pubmed: 9491800
J Cell Biol. 1998 Dec 14;143(6):1415-25
pubmed: 9852140
Nucleic Acids Res. 2005 Jun 21;33(11):3521-8
pubmed: 15972794
Cell. 1982 Oct;30(3):687-96
pubmed: 7139712
Nature. 2002 Dec 5;420(6915):520-62
pubmed: 12466850