@article{Hiratani01022010,
author = {Hiratani, Ichiro and Ryba, Tyrone and Itoh, Mari and Rathjen, Joy and Kulik, Michael and Papp, Bernadett and Fussner, Eden and Bazett-Jones, David P. and Plath, Kathrin and Dalton, Stephen and Rathjen, Peter D. and Gilbert, David M.}, 
title = {Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis},
volume = {20}, 
number = {2}, 
pages = {155-169}, 
year = {2010}, 
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 post-implantation 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 early-to-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.}, 
URL = {http://genome.cshlp.org/content/20/2/155.abstract}, 
eprint = {http://genome.cshlp.org/content/20/2/155.full.pdf+html}, 
journal = {Genome Research} 
}