TUdatalib : Developmental differences in genome replication program and origin activation

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dc.contributor.author	Rausch, Cathia
dc.contributor.author	Weber, Patrick
dc.contributor.author	Prorok, Paulina
dc.contributor.author	Hörl, David
dc.contributor.author	Maiser, Andreas
dc.contributor.author	Lehmkuhl, Anne
dc.contributor.author	Chagin, Vadim O.
dc.contributor.author	Casas-Delucchi, Corella S
dc.contributor.author	Leonhardt, Heinrich
dc.contributor.author	Cardoso, M. Cristina
dc.date.accessioned	2020-06-30T14:42:59Z
dc.date.available	2020-06-30T14:42:59Z
dc.date.issued	2020-06-30
dc.identifier.uri	https://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/2376
dc.identifier.uri	https://doi.org/10.25534/tudatalib-220
dc.description	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 correlating with increase in condensation and decrease in acetylation of chromatin. We also 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 in mES cells versus somatic cells. We conclude that each replication nanofocus in mES cells corresponds to an individual replicon, with approximately 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.	en_US
dc.language.iso	en	en_US
dc.rights	Creative Commons Attribution-NonCommercial 4.0
dc.rights.uri	https://creativecommons.org/licenses/by-nc/4.0/
dc.subject	DNA replication	en_US
dc.subject	origin activation	en_US
dc.subject	replication timing	en_US
dc.subject	embryonic stem cells	en_US
dc.subject.classification	2.11-03 Zellbiologie	en_US
dc.subject.ddc	570
dc.title	Developmental differences in genome replication program and origin activation	en_US
dc.type	Text	en_US
dc.type	Software	en_US
dc.type	Image	en_US
tud.project	DFG \| CA198/9-2 \| Hochauflösende Analy	en_US
tud.project	DFG \| CA198/12-1 \| Einfluss von DNA-Bas	en_US
tud.project	DFG \| SFB1361,TP06 \| TP_06_Cardoso_Mainz
tud.history.classification	Version=2020-2024;201-03 Zellbiologie