Ontology highlight
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PROVIDER: PRJNA722362 | ENA |
REPOSITORIES: ENA
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Project description:Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity of our genome. Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0.4% of the mouse genome with detailed molecular analysis at distinct classes of ORIs according to their location relative to the genes. Our study reveals that 85% of the replication initiation sites in mouse embryonic stem (ES) cells are associated with transcriptional units. Nearly half of the identified ORIs map at promoter regions and, interestingly, ORI density strongly correlates with promoter density, reflecting the coordinated organisation of replication and transcription in the mouse genome. Detailed analysis of ORI activity showed that CpG island promoter-ORIs are the most efficient ORIs in ES cells and both ORI specification and firing efficiency are maintained across cell types. Remarkably, the distribution of replication initiation sites at promoter-ORIs exactly parallels that of transcription start sites (TSS) suggesting a co-evolution of the regulatory regions driving replication and transcription. Moreover, we found that promoter-ORIs are significantly enriched in CAGE tags derived from early embryos relative to all promoters. This association implies that transcription initiation early in development sets the probability of ORI activation unveiling a new hallmark in ORI efficiency regulation in mammalian cells. Two biological replicates of lambda-exonuclease treated short nascent strands (100-600 or 300-800 nt in length) were co-hybridised with genomic DNA from the same cells to tiled genomic array covering 10.1 Mb of the mouse genome (Agilent Technologies)
2010-05-22 | E-GEOD-15082 | biostudies-arrayexpress
Project description:Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity of our genome. Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0.4% of the mouse genome with detailed molecular analysis at distinct classes of ORIs according to their location relative to the genes. Our study reveals that 85% of the replication initiation sites in mouse embryonic stem (ES) cells are associated with transcriptional units. Nearly half of the identified ORIs map at promoter regions and, interestingly, ORI density strongly correlates with promoter density, reflecting the coordinated organisation of replication and transcription in the mouse genome. Detailed analysis of ORI activity showed that CpG island promoter-ORIs are the most efficient ORIs in ES cells and both ORI specification and firing efficiency are maintained across cell types. Remarkably, the distribution of replication initiation sites at promoter-ORIs exactly parallels that of transcription start sites (TSS) suggesting a co-evolution of the regulatory regions driving replication and transcription. Moreover, we found that promoter-ORIs are significantly enriched in CAGE tags derived from early embryos relative to all promoters. This association implies that transcription initiation early in development sets the probability of ORI activation unveiling a new hallmark in ORI efficiency regulation in mammalian cells.
2009-03-05 | GSE15082 | GEO
Project description:Full genome replication in eukaryotes depends on the function of thousands of DNA replication origins (ORIs). The genome-wide identification of ORI location, achieved for animal and plant cells in culture, has been important to define their DNA and chromatin features. A major challenge in the field is to approach the biology of ORIs in whole organisms to understand their developmental plasticity. Here, we have determined the ORI location, activity and chromatin landscape in two developmental stages of Arabidopsis thaliana. We found that ORIs associate with multiple chromatin signatures including the most frequent at TSS but also at proximal and distal gene regulatory regions or repressed Polycomb domains. In constitutive heterochromatin, a high fraction of ORIs colocalize with GC-rich retrotransposons. Quantitative analysis of ORI activity led us to conclude that strong ORIs possess high scores of local GC content and clusters of GGN trinucleotides that may form G quadruplexes and other G-rich structures. We also found that development primarily influences ORI firing strength rather than the location of ORIs in different genomic loci. Moreover, ORIs that preferentially fire at early vegetative stages colocalize with GC-rich heterochromatin whereas those at later stages associate with transcribed genes. Our results provide the first identification of ORI features in a whole organism, opening new ways of studying DNA replication in different cell types in the context of development under normal and mutant conditions.
2018-04-15 | GSE109668 | GEO
Project description:Replication of plasmids without Ori into Thermococcus barophilus suggest utilization of recombination-dependent replication
| PRJEB40197 | ENA
Project description:In metazoans, thousands of DNA replication origins (Oris) are activated to replicate DNA at each cell cycle. Although their timing of activation is better understood, their genomic organization and their genetic nature remain elusive. Here, we identified Oris by nascent strand (NS) purification and characterized their common features by performing a genome-wide analysis in both Drosophila and mouse cell lines. We show that in both species most CpG islands (CGI) contain Oris, although methylation is nearly absent in Drosophila, suggesting that this epigenetic mark is not crucial for defining the initiation event. Moreover, nascent strands at the borders of CGIs show a striking bimodal distribution, suggestive of a dual initiation event. We also found that Oris contain a unique nucleotide skew around NS peaks, characterized by G/T and C/A over-representation at 5’ and 3’ of the Ori sites, respectively. GC-rich elements are detected, which are good predictors of Oris, in both mouse and Drosophila, suggesting that common sequence features are part of metazoan Oris. In the heterochromatic chromosome 4 of Drosophila, Oris are strongly correlated with HP1 binding sites. At the chromosome level, we show that Oris are organized in Ori-rich and -poor regions that co-localize with early and late replicating domains, respectively. Finally, the genome-wide analysis was coupled with a DNA combing analysis of the in-vivo spacing of replication origins. The results suggest that Oris are in large excess, and organized in groups of site-specific but flexible origins that define replicons, where a single origin is used in each group. This organization provides both site specificity and Ori firing flexibility in each replicon, allowing possible adaptation of DNA replication to environmental cues and cell fates.
2011-07-28 | GSE29183 | GEO
Project description:Analysis of WT-Ctl v.s. WT-Ori and R878H-Ctl v.s. R878H-Ori hematopoietic stem cell (lineage-, c-kit+ Sca-1+ CD150+, CD34-). The four population of hematopoietic stem cell (HSC) were purified from the bone marrow of WT and R878H recipent mice treated with vehicle or oridonin. Results provide insight into the role of oridonin in R878H HSC.
2021-05-13 | GSE174362 | GEO
Project description:The human epithelial follicular cell line Nthy-ori 3-1 was treated with 10 uM or 1 uM benzo[a]pyrene in 0.5% DMSO or with 0.5% DMSO only for 24 hours. Thyroid follicles were differentiated from a recombinant mESC line (A2LoxNkx2-1-Pax8) and treated with 0.5% DMSO for 24 hours. For Nthy-ori 3-1 samples, total RNA was extracted and used to prepare combined mRNA/miRNA libraries, poly(A) libraries and small RNA libraries. For thyroid follicles samples, total RNA was extracted and used to prepare combined mRNA/miRNA libraries.
2022-12-14 | E-MTAB-12078 | biostudies-arrayexpress
Project description:Paper abstract : The Escherichia coli SMC complex, MukBEF, interacts with the ParC subunit of topoisomerase IV (TopoIV), consistent with sequential roles in chromosome unlinking and segregation. Although clusters of MukBEF molecules are normally associated with the chromosome replication origin region (ori), we demonstrate their association with the replication termination region (ter), which is enhanced when ATP hydrolysis by MukB is impaired. We show that MukBEF interacts in vivo and in vitro with MatP, which binds matS sites in ter. The MatP-MukBEF interaction limits the stable association of MukBEF complexes with ter and the availability of functional TopoIV during decatenation of sister ters. The MukBEF-TopoIV interaction is influenced by the nucleotide state of MukBEF. The combined action of MukBEF and MatP helps position MukBEF clusters in relation to the chromosome, thereby, influencing chromosome organization and segregation. Finally, we demonstrate that the regulated sequential action of TopoIV and MukBEF promotes chromosome decatenation and segregation.
2016-01-28 | GSE67221 | GEO
Project description:Bacterial species from diverse phyla contain multiple replicons, yet how these multipartite genomes are organized and segregated during the cell cycle remains poorly understood. Agrobacterium tumefaciens has a 2.8 Mb circular chromosome (Ch1), a 2.1 Mb linear chromosome (Ch2), and two large plasmids (pAt and pTi). We used this alpha proteobacterium as a model to investigate the global organization and temporal segregation of a multipartite genome. Using Chromosome Conformation Capture (Hi-C) assays, we demonstrate that both the circular and the linear chromosomes but neither of the plasmids have their left and right arms juxtaposed from their origins to their termini, generating inter-arm interactions that require the broadly conserved structural maintenance of chromosomes (SMC) complex. Moreover, our studies revealed two types of inter-replicon interactions: “ori-ori clustering” in which the replication origins of all four replicons interact, and “Ch1-Ch2 alignment” in which the arms of Ch1 and Ch2 interact linearly along their lengths. We show that the centromeric proteins (ParB1 for Ch1 and RepBCh2 for Ch2) are required for both types of inter-replicon contacts. Finally, using fluorescence microscopy, we validated the clustering of the origins and observed their frequent colocalization during segregation. Altogether, our findings provide a high-resolution view of the conformation of a multipartite genome. We hypothesize that inter-centromeric contacts promote the organization and maintenance of diverse replicons.
2022-01-30 | GSE182881 | GEO
Project description:Somatic CNV profile of congenital ectopic thyroids
| PRJNA118741 | ENA