Superresolution imaging reveals spatiotemporal propagation of human replication foci mediated by CTCF-organized chromatin structures.

Su, QP; Zhao, ZW; Meng, L; Ding, M; Zhang, W; Li, Y; Liu, M; Li, R; Gao, Y-Q; Xie, XS; Sun, Y

Superresolution imaging reveals spatiotemporal propagation of human replication foci mediated by CTCF-organized chromatin structures.

Su, QP Zhao, ZW Meng, L Ding, M Zhang, W Li, Y Liu, M Li, R Gao, Y-Q Xie, XS Sun, Y

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Publisher:: Proceedings of the National Academy of Sciences
Publication Type:: Journal Article
Citation:: Proceedings of the National Academy of Sciences of the United States of America, 2020, 117, (26), pp. 15036-15046
Issue Date:: 2020-06-15

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Field	Value	Language
dc.contributor.author	Su, QP
dc.contributor.author	Zhao, ZW
dc.contributor.author	Meng, L
dc.contributor.author	Ding, M
dc.contributor.author	Zhang, W
dc.contributor.author	Li, Y
dc.contributor.author	Liu, M
dc.contributor.author	Li, R
dc.contributor.author	Gao, Y-Q
dc.contributor.author	Xie, XS
dc.contributor.author	Sun, Y
dc.date.accessioned	2020-10-21T05:43:22Z
dc.date.available	2020-10-21T05:43:22Z
dc.date.issued	2020-06-15
dc.identifier.citation	Proceedings of the National Academy of Sciences of the United States of America, 2020, 117, (26), pp. 15036-15046
dc.identifier.issn	0027-8424
dc.identifier.issn	1091-6490
dc.identifier.uri	http://hdl.handle.net/10453/143434
dc.description.abstract	Mammalian DNA replication is initiated at numerous replication origins, which are clustered into thousands of replication domains (RDs) across the genome. However, it remains unclear whether the replication origins within each RD are activated stochastically or preferentially near certain chromatin features. To understand how DNA replication in single human cells is regulated at the sub-RD level, we directly visualized and quantitatively characterized the spatiotemporal organization, morphology, and in situ epigenetic signatures of individual replication foci (RFi) across S-phase at superresolution using stochastic optical reconstruction microscopy. Importantly, we revealed a hierarchical radial pattern of RFi propagation dynamics that reverses directionality from early to late S-phase and is diminished upon caffeine treatment or CTCF knockdown. Together with simulation and bioinformatic analyses, our findings point to a "CTCF-organized REplication Propagation" (CoREP) model, which suggests a nonrandom selection mechanism for replication activation at the sub-RD level during early S-phase, mediated by CTCF-organized chromatin structures. Collectively, these findings offer critical insights into the key involvement of local epigenetic environment in coordinating DNA replication across the genome and have broad implications for our conceptualization of the role of multiscale chromatin architecture in regulating diverse cell nuclear dynamics in space and time.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Proceedings of the National Academy of Sciences
dc.relation	http://purl.org/au-research/grants/nhmrc/1177374
dc.relation.ispartof	Proceedings of the National Academy of Sciences of the United States of America
dc.relation.isbasedon	10.1073/pnas.2001521117
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.mesh	CCCTC-Binding Factor
dc.subject.mesh	Chromatin
dc.subject.mesh	DNA Replication
dc.subject.mesh	Epigenomics
dc.subject.mesh	Humans
dc.subject.mesh	S Phase
dc.title	Superresolution imaging reveals spatiotemporal propagation of human replication foci mediated by CTCF-organized chromatin structures.
dc.type	Journal Article
utslib.citation.volume	117
utslib.location.activity	United States
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2020-10-21T05:43:04Z
pubs.issue	26
pubs.publication-status	Published
pubs.volume	117
utslib.citation.issue	26

Abstract:

Mammalian DNA replication is initiated at numerous replication origins, which are clustered into thousands of replication domains (RDs) across the genome. However, it remains unclear whether the replication origins within each RD are activated stochastically or preferentially near certain chromatin features. To understand how DNA replication in single human cells is regulated at the sub-RD level, we directly visualized and quantitatively characterized the spatiotemporal organization, morphology, and in situ epigenetic signatures of individual replication foci (RFi) across S-phase at superresolution using stochastic optical reconstruction microscopy. Importantly, we revealed a hierarchical radial pattern of RFi propagation dynamics that reverses directionality from early to late S-phase and is diminished upon caffeine treatment or CTCF knockdown. Together with simulation and bioinformatic analyses, our findings point to a "CTCF-organized REplication Propagation" (CoREP) model, which suggests a nonrandom selection mechanism for replication activation at the sub-RD level during early S-phase, mediated by CTCF-organized chromatin structures. Collectively, these findings offer critical insights into the key involvement of local epigenetic environment in coordinating DNA replication across the genome and have broad implications for our conceptualization of the role of multiscale chromatin architecture in regulating diverse cell nuclear dynamics in space and time.

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http://hdl.handle.net/10453/143434