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Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis

Citation

Hiratani, I and Ryba, T and Itoh, M and Rathjen, J and Kulik, M and Papp, B and Fussner, E and Bazett-Jones, D and Plath, K and Dalton, S and Rathjen, PD and Gilbert, DM, Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis, Genome Research, 20, (2) pp. 155-169. ISSN 1088-9051 (2010) [Refereed Article]

DOI: doi:10.1101/gr.099796.109

Abstract

Differentiation of mouse embryonic stem cells (mESCs) is accompanied by changes in replication timing. To explore the relationship between replication timing and cell fate transitions, we constructed genome-wide replication-timing profiles of 22 independent mouse cell lines representing 10 stages of early mouse development, and transcription profiles for seven of these stages. Replication profiles were cell-type specific, with 45% of the genome exhibiting significant changes at some point during development that were generally coordinated with changes in transcription. Comparison of early and late epiblast cell culture models revealed a set of early-to-late replication switches completed at a stage equivalent to the postimplantation epiblast, prior to germ layer specification and down-regulation of key pluripotency transcription factors [POU5F1 (also known as OCT4)/NANOG/SOX2] and coinciding with the emergence of compact chromatin near the nuclear periphery. These changes were maintained in all subsequent lineages (lineage-independent) and involved a group of irreversibly down-regulated genes, at least some of which were repositioned closer to the nuclear periphery. Importantly, many genomic regions of partially reprogrammed induced pluripotent stem cells (piPSCs) failed to re-establish ESC-specific replication-timing and transcription programs. These regions were enriched for lineage-independent earlyto-late changes, which in female cells included the inactive X chromosome. Together, these results constitute a comprehensive "fate map" of replication-timing changes during early mouse development. Moreover, they support a model in which a distinct set of replication domains undergoes a form of "autosomal Lyonization" in the epiblast that is difficult to reprogram and coincides with an epigenetic commitment to differentiation prior to germ layer specification. © 2010 by Cold Spring Harbor Laboratory Press.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Development, Proliferation and Death
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Rathjen, J (Dr Joy Rathjen)
Author:Rathjen, PD (Professor Peter Rathjen)
ID Code:78725
Year Published:2010
Web of Science® Times Cited:161
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-07-24
Last Modified:2014-08-25
Downloads:0

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