Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency

Li, Y; Xue, B; Zhang, M; Zhang, L; Hou, Y; Qin, Y; Long, H; Su, QP; Wang, Y; Guan, X; Jin, Y; Cao, Y; Li, G; Sun, Y

Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency

Li, Y Xue, B Zhang, M Zhang, L Hou, Y Qin, Y Long, H Su, QP Wang, Y Guan, X Jin, Y Cao, Y Li, G Sun, Y

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Publisher:: BioMed Central
Publication Type:: Journal Article
Citation:: Genome Biology, 2021, 22, (1), pp. 1-29
Issue Date:: 2021-07-12

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Field	Value	Language
dc.contributor.author	Li, Y
dc.contributor.author	Xue, B
dc.contributor.author	Zhang, M
dc.contributor.author	Zhang, L
dc.contributor.author	Hou, Y
dc.contributor.author	Qin, Y
dc.contributor.author	Long, H
dc.contributor.author	Su, QP
dc.contributor.author	Wang, Y
dc.contributor.author	Guan, X
dc.contributor.author	Jin, Y
dc.contributor.author	Cao, Y
dc.contributor.author	Li, G
dc.contributor.author	Sun, Y
dc.date.accessioned	2022-05-30T02:26:46Z
dc.date.available	2021-06-30
dc.date.available	2022-05-30T02:26:46Z
dc.date.issued	2021-07-12
dc.identifier.citation	Genome Biology, 2021, 22, (1), pp. 1-29
dc.identifier.issn	1474-7596
dc.identifier.issn	1474-760X
dc.identifier.uri	http://hdl.handle.net/10453/157814
dc.description.abstract	Background Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined. Results We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired. Conclusion Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics.
dc.format	Electronic
dc.language	eng
dc.publisher	BioMed Central
dc.relation	National Heart Foundation of Australia102592
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1177374
dc.relation	http://purl.org/au-research/grants/arc/DP200101970
dc.relation	http://purl.org/au-research/grants/nhmrc/APP2003904
dc.relation.ispartof	Genome Biology
dc.relation.isbasedon	10.1186/s13059-021-02424-w
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	05 Environmental Sciences, 06 Biological Sciences, 08 Information and Computing Sciences
dc.subject.classification	Bioinformatics
dc.subject.mesh	CCCTC-Binding Factor
dc.subject.mesh	Cell Cycle Proteins
dc.subject.mesh	Cell Line
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Chromatin
dc.subject.mesh	Chromatin Assembly and Disassembly
dc.subject.mesh	DNA Replication
dc.subject.mesh	DNA-Binding Proteins
dc.subject.mesh	G1 Phase Cell Cycle Checkpoints
dc.subject.mesh	Gene Expression
dc.subject.mesh	HeLa Cells
dc.subject.mesh	Humans
dc.subject.mesh	In Situ Hybridization, Fluorescence
dc.subject.mesh	Optical Imaging
dc.subject.mesh	Osteoblasts
dc.subject.mesh	Proliferating Cell Nuclear Antigen
dc.subject.mesh	RNA, Small Interfering
dc.subject.mesh	Replication Origin
dc.subject.mesh	Retinal Pigment Epithelium
dc.subject.mesh	Transcription, Genetic
dc.subject.mesh	Cell Line
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Hela Cells
dc.subject.mesh	Chromatin
dc.subject.mesh	Osteoblasts
dc.subject.mesh	Humans
dc.subject.mesh	Cell Cycle Proteins
dc.subject.mesh	DNA-Binding Proteins
dc.subject.mesh	Proliferating Cell Nuclear Antigen
dc.subject.mesh	RNA, Small Interfering
dc.subject.mesh	In Situ Hybridization, Fluorescence
dc.subject.mesh	Chromatin Assembly and Disassembly
dc.subject.mesh	DNA Replication
dc.subject.mesh	Gene Expression
dc.subject.mesh	Transcription, Genetic
dc.subject.mesh	Replication Origin
dc.subject.mesh	Retinal Pigment Epithelium
dc.subject.mesh	G1 Phase Cell Cycle Checkpoints
dc.subject.mesh	Optical Imaging
dc.subject.mesh	CCCTC-Binding Factor
dc.title	Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency
dc.type	Journal Article
utslib.citation.volume	22
utslib.location.activity	England
utslib.for	05 Environmental Sciences
utslib.for	06 Biological Sciences
utslib.for	08 Information and Computing Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-05-30T02:26:44Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	22
utslib.citation.issue	1

Abstract:

Background Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined. Results We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired. Conclusion Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/157814