Genome-Wide Dynamics of Replication Timing Revealed by In Vitro Models of Mouse Embryogenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE18019 | GEO | 2009/11/25
SECONDARY ACCESSION(S): PRJNA119253
REPOSITORIES: GEO
Similar Datasets
Project description: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.
| S-EPMC2813472 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE17980: Genome-Wide Dynamics of Replication Timing Revealed by In Vitro Models of Mouse Embryogenesis (Expression) GSE17983: Genome-Wide Dynamics of Replication Timing Revealed by In Vitro Models of Mouse Embryogenesis (WG_CGH; Replication Timing) GSE17980 (Expression): 8 cell lines, with a total of 14 individual replicates (i.e. 6 in duplicates, 2 in single replicates) GSE17983 (WG_CGH; Replication Timing): 22 cell lines, with a total of 36 individual replicates (i.e. 14 in duplicates, 8 in single replicates)
2010-05-19 | E-GEOD-18019 | biostudies-arrayexpress
Project description: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 lineage-independent 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 (Oct4/Nanog/Sox2) and coinciding with the emergence of compact chromatin near the nuclear periphery. These changes were conserved in all subsequent lineages 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. Taken together, we demonstrate that replication-timing changes are extensive during development. Moreover, a distinct set of lineage-independent, early-to-late changes completed in and stably maintained after the post-implantation epiblast stage is difficult to reprogram and therefore coincides with an epigenetic commitment to differentiation prior to germ layer specification. 8 cell lines, with a total of 14 individual replicates (i.e. 6 in duplicates, 2 in single replicates)
2010-05-19 | E-GEOD-17980 | biostudies-arrayexpress
Project description: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 lineage-independent 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 (Oct4/Nanog/Sox2) and coinciding with the emergence of compact chromatin near the nuclear periphery. These changes were conserved in all subsequent lineages 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. Taken together, we demonstrate that replication-timing changes are extensive during development. Moreover, a distinct set of lineage-independent, early-to-late changes completed in and stably maintained after the post-implantation epiblast stage is difficult to reprogram and therefore coincides with an epigenetic commitment to differentiation prior to germ layer specification.
2009-11-25 | GSE17980 | GEO
Project description:Genome-Wide Dynamics of Replication Timing Revealed by In Vitro Models of Mouse Embryogenesis
| PRJNA119253 | ENA
Project description:Microarrays are powerful tools to probe genome-wide replication kinetics. The rich data sets that result contain more information than has been extracted by current methods of analysis. In this paper, we present an analytical model that incorporates probabilistic initiation of origins and passive replication. Using the model, we performed least-squares fits to a set of recently published time course microarray data on Saccharomyces cerevisiae. We extracted the distribution of firing times for each origin and found that the later an origin fires on average, the greater the variation in firing times. To explain this trend, we propose a model where earlier-firing origins have more initiator complexes loaded and a more accessible chromatin environment. The model demonstrates how initiation can be stochastic and yet occur at defined times during S phase, without an explicit timing program. Furthermore, we hypothesize that the initiators in this model correspond to loaded minichromosome maintenance complexes. This model is the first to suggest a detailed, testable, biochemically plausible mechanism for the regulation of replication timing in eukaryotes.
| S-EPMC2950085 | biostudies-other
Project description:Replication timing is cell type specific, is tightly linked to the 3D nuclear organisation of the genome and is considered an epigenetic fingerprint. In spite of its importance in maintaining the epigenome the developmental regulation of replication timing in mammals in vivo has not been explored. Here, using single cell Repli-seq, we generated the genome-wide replication timing maps of mouse embryos from the zygote until the blastocyst stage.
2023-10-16 | GSE218365 | GEO
Project description:Developing stickleback embryos were dissociated and sorted for S-phase and G0/G1-phase cell populations. DNA was extracted from each population and sequenced. In a mixed S-phase population, regions that replicate earlier are at higher copy number (up to 2x) than regions that replicate later. The read depth in S-phase, normalized to the read depth in G-phase, thus represents replication timing.
2018-10-20 | GSE121537 | GEO
Project description:DNA replication is initiated at multiple sites or origins enriched with AT-rich sequences at various times during the S-phase. While current studies of genome-wide DNA replication profiles have focused on the timing of replication and the location of origins, the efficiency of replication/firing at various origins remains unclear. In this study, we show different efficiencies of DNA replication at various loci by using ORF-specific DNA microarrays. DNA copy-number increases as a function of time at individual loci are approximated to near-sigmoidal models for estimation of replication initiation and completion timings in HU-challenged cells. Duplicating times (from initiation to completion) vary from loci to loci, partly contributing to various firing efficiencies at origins. DNA replication timing profiles are strikingly similar to the reported patterns of enriched ssDNA, suggesting that majority stalled forks are restored for resumption of DNA replication. Although the DNA replication timing profiles are disrupted in HU-challenged cds1? cells, ~85% of potential origins overlapped with those found in wild type cells, significantly, most of which represents inefficiently fired origins in wild type cells. Together, our result indicates that replication checkpoint plays a role in monitoring efficient origins and thus maintaining global DNA replication patterns in HU-challenged cells. Keywords: WT or Cds1 HU synchronized cells released in HU free media and harvested at different time points vs WT or Cds1 synchronized with HU for 3 hrs. We analyzed 32 arrays for WT and 38 arrays for Cds1 cells which were synchronized with HU and released in HU free media and harvested at different time points. At least two biological repeats were done for each time points.
2007-08-14 | E-GEOD-6977 | biostudies-arrayexpress
Project description:The agnostic screening performed by genome-wide association studies (GWAS) has uncovered associations for previously unsuspected genes. Knowledge about the functional role of these genes is crucial and laboratory mouse models can provide such information. Here, we describe a systematic juxtaposition of human GWAS-discovered loci versus mouse models in order to appreciate the availability of mouse models data, to gain biological insights for the role of these genes and to explore the extent of concordance between these two lines of evidence. We perused publicly available data (NHGRI database for human associations and Mouse Genome Informatics database for mouse models) and employed two alternative approaches for cross-species comparisons, phenotype- and gene-centric. A total of 293 single gene-phenotype human associations (262 unique genes and 69 unique phenotypes) were evaluated. In the phenotype-centric approach, we identified all mouse models and related ortholog genes for the 51 human phenotypes with a comparable phenotype in mice. A total of 27 ortholog genes were found to be associated with the same phenotype in humans and mice, a concordance that was significantly larger than expected by chance (p<0.001). In the gene-centric approach, we were able to locate at least 1 knockout model for 60% of the 262 genes. The knockouts for 35% of these orthologs displayed pre- or post-natal lethality. For the remaining non-lethal orthologs, the same organ system was involved in mice and humans in 71% of the cases (p<0.001). Our project highlights the wealth of available information from mouse models for human GWAS, catalogues extensive information on plausible physiologic implications for many genes, provides hypothesis-generating findings for additional GWAS analyses and documents that the concordance between human and mouse genetic association is larger than expected by chance and can be informative.
| S-EPMC2967475 | biostudies-literature