Preferential localization of human origins of DNA replication at the 5' end of expressed genes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE10917 | GEO | 2011/05/13
SECONDARY ACCESSION(S): PRJNA107217
REPOSITORIES: GEO
Similar Datasets
Project description:Human DNA replication relies on the activation of thousands of origins distributed along the genome. Their organization and the functional significance of their distribution remains unknown. To map large number of origins in human cells, we have localized the distribution of short nascent DNA using a high-resolution DNA tiling array platform covering 33.9Mb. Results with three different cell lines reveal that origins are very closely spaced (average interval 3-5kb), and that their positions are largely conserved among the cell lines studied. Origins are non-randomly distributed, being preferentially enriched at the 5’-end of expressed genes and at evolutionary intergenic sequences. In MCF7 cells, a strong correlation is also found between origin positioning and histone H3K4me3 and of PolII binding to chromatin. This study provides a large scale view of the organization of DNA replication origins in human chromosomes and suggests a link between this distribution and underlying chromatin features related to chromosome structure, and gene expression Keywords: nascent strand DNA, histone, Pol-II ChIP-chip. To map initiation sites for DNA replication and the position of both H3K4Me3 and Pol-II chromatin binding sites in human cell lines on a custom made high density tiling DNA microarray covering 33.9 Mb of the human genome.
2011-05-13 | E-GEOD-10917 | biostudies-arrayexpress
Project description:Genomic integrity requires faithful chromosome duplication. Origins of replication are the genomic sites where DNA replication initiates in every cell cycle. There are multiple origins scattered throughout the eukaryotic genome whose genome-wide identification has been a hard challenge, especially in multicellular organisms. Thus, very little is known on the distinctive features of origins in terms of DNA sequence and chromatin context at a genomic scale. Here we have profiled origins in Arabidopsis thaliana by high-throughput sequencing of purified nascent DNA strands. We have identified 1543 replication origins, which were uniformly distributed across the Arabidopsis genome and enriched in binding signals of two replication initiation proteins, CDC6 and ORC1. We have also analyzed novel epigenome maps of various histone modifications and found links between origins and epigenetic signatures, which differ from or have not been reported for other eukaryotic systems. Arabidopsis origins tend to be embedded in G+C-rich regions within the 5’ half of genes, enriched in histone H2A.Z, H3K4me2/3 and acetylated H3 and H4, and depleted of H3K4me1 and H3K9me2. Our data establish the basis for the understanding of the epigenetic specification of origins of replication in Arabidopsis and have implications for the mechanisms of origin specification in other eukaryotes. Examination of BrdU labelled DNA and unlabelled DNA in one cell type
2011-11-06 | E-GEOD-21781 | biostudies-arrayexpress
Project description:Genomic integrity requires faithful chromosome duplication. Origins of replication are the genomic sites where DNA replication initiates in every cell cycle. There are multiple origins scattered throughout the eukaryotic genome whose genome-wide identification has been a hard challenge, especially in multicellular organisms. Thus, very little is known on the distinctive features of origins in terms of DNA sequence and chromatin context at a genomic scale. Here we have profiled origins in Arabidopsis thaliana by high-throughput sequencing of purified nascent DNA strands. We have identified 1543 replication origins, which were uniformly distributed across the Arabidopsis genome and enriched in binding signals of two replication initiation proteins, CDC6 and ORC1. We have also analyzed novel epigenome maps of various histone modifications and found links between origins and epigenetic signatures, which differ from or have not been reported for other eukaryotic systems. Arabidopsis origins tend to be embedded in G+C-rich regions within the 5M-bM-^@M-^Y half of genes, enriched in histone H2A.Z, H3K4me2/3 and acetylated H4, and depleted of H3K4me1 and H3K9me2. Our data establish the basis for the understanding of the epigenetic specification of origins of replication in Arabidopsis and have implications for the mechanisms of origin specification in other eukaryotes. This SuperSeries is composed of the following subset Series: GSE21781: Mapping origins of replication in Arabidopsis thaliana: Examination of BrdU labelled DNA and unlabelled DNA in one cell type GSE21827: Mapping origins of replication in Arabidopsis thaliana: H3K4ac ChIP vs. unmodified H3 ChIP Refer to individual Series
2011-02-06 | E-GEOD-21828 | biostudies-arrayexpress
Project description:Genomic integrity requires faithful chromosome duplication. Origins of replication are the genomic sites where DNA replication initiates in every cell cycle. There are multiple origins scattered throughout the eukaryotic genome whose genome-wide identification has been a hard challenge, especially in multicellular organisms. Thus, very little is known on the distinctive features of origins in terms of DNA sequence and chromatin context at a genomic scale. Here we have profiled origins in Arabidopsis thaliana by high-throughput sequencing of purified nascent DNA strands. We have identified 1543 replication origins, which were uniformly distributed across the Arabidopsis genome and enriched in binding signals of two replication initiation proteins, CDC6 and ORC1. We have also analyzed novel epigenome maps of various histone modifications and found links between origins and epigenetic signatures, which differ from or have not been reported for other eukaryotic systems. Arabidopsis origins tend to be embedded in G+C-rich regions within the 5M-bM-^@M-^Y half of genes, enriched in histone H2A.Z, H3K4me2/3 and acetylated H3 and H4, and depleted of H3K4me1 and H3K9me2. Our data establish the basis for the understanding of the epigenetic specification of origins of replication in Arabidopsis and have implications for the mechanisms of origin specification in other eukaryotes. H4K5ac ChIP vs. unmodified H3 ChIP. Our study utilizes the following datasets in addition to the data we generated: H3K4me1: GSM343141 H3K4me2: GSM343143 H3K4me3: GSM343144 H3K9me2: GSM310840 H2AZ: GSM307373
2011-11-06 | E-GEOD-21827 | biostudies-arrayexpress
Project description:Genomic integrity requires faithful chromosome duplication. Origins of replication are the genomic sites where DNA replication initiates in every cell cycle. There are multiple origins scattered throughout the eukaryotic genome whose genome-wide identification has been a hard challenge, especially in multicellular organisms. Thus, very little is known on the distinctive features of origins in terms of DNA sequence and chromatin context at a genomic scale. Here we have profiled origins in Arabidopsis thaliana by high-throughput sequencing of purified nascent DNA strands. We have identified 1543 replication origins, which were uniformly distributed across the Arabidopsis genome and enriched in binding signals of two replication initiation proteins, CDC6 and ORC1. We have also analyzed novel epigenome maps of various histone modifications and found links between origins and epigenetic signatures, which differ from or have not been reported for other eukaryotic systems. Arabidopsis origins tend to be embedded in G+C-rich regions within the 5’ half of genes, enriched in histone H2A.Z, H3K4me2/3 and acetylated H3 and H4, and depleted of H3K4me1 and H3K9me2. Our data establish the basis for the understanding of the epigenetic specification of origins of replication in Arabidopsis and have implications for the mechanisms of origin specification in other eukaryotes.
2011-11-06 | GSE21827 | GEO
Project description:Genomic integrity requires faithful chromosome duplication. Origins of replication are the genomic sites where DNA replication initiates in every cell cycle. There are multiple origins scattered throughout the eukaryotic genome whose genome-wide identification has been a hard challenge, especially in multicellular organisms. Thus, very little is known on the distinctive features of origins in terms of DNA sequence and chromatin context at a genomic scale. Here we have profiled origins in Arabidopsis thaliana by high-throughput sequencing of purified nascent DNA strands. We have identified 1543 replication origins, which were uniformly distributed across the Arabidopsis genome and enriched in binding signals of two replication initiation proteins, CDC6 and ORC1. We have also analyzed novel epigenome maps of various histone modifications and found links between origins and epigenetic signatures, which differ from or have not been reported for other eukaryotic systems. Arabidopsis origins tend to be embedded in G+C-rich regions within the 5’ half of genes, enriched in histone H2A.Z, H3K4me2/3 and acetylated H3 and H4, and depleted of H3K4me1 and H3K9me2. Our data establish the basis for the understanding of the epigenetic specification of origins of replication in Arabidopsis and have implications for the mechanisms of origin specification in other eukaryotes.
2011-11-06 | GSE21781 | GEO
Project description:Genomic integrity requires faithful chromosome duplication. Origins of replication are the genomic sites where DNA replication initiates in every cell cycle. There are multiple origins scattered throughout the eukaryotic genome whose genome-wide identification has been a hard challenge, especially in multicellular organisms. Thus, very little is known on the distinctive features of origins in terms of DNA sequence and chromatin context at a genomic scale. Here we have profiled origins in Arabidopsis thaliana by high-throughput sequencing of purified nascent DNA strands. We have identified 1543 replication origins, which were uniformly distributed across the Arabidopsis genome and enriched in binding signals of two replication initiation proteins, CDC6 and ORC1. We have also analyzed novel epigenome maps of various histone modifications and found links between origins and epigenetic signatures, which differ from or have not been reported for other eukaryotic systems. Arabidopsis origins tend to be embedded in G+C-rich regions within the 5’ half of genes, enriched in histone H2A.Z, H3K4me2/3 and acetylated H4, and depleted of H3K4me1 and H3K9me2. Our data establish the basis for the understanding of the epigenetic specification of origins of replication in Arabidopsis and have implications for the mechanisms of origin specification in other eukaryotes. This SuperSeries is composed of the SubSeries listed below.
2011-02-06 | GSE21828 | GEO
Project description:Faithful inheritance of the large eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins. Although origin activation is mechanistically conserved among eukaryotes, how replication origins are specified and selected for activation in each S-phase seem to differ across the model systems studied. Here we provide a complete analysis of the nucleosomal landscape and replication programme of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of L. major genome, and that both the spatial and the temporal programme of DNA replication can be explained as associated to RNA polymerase kinetics, without the need to invoke specific regulatory mechanisms. This simple scenario likely provides these organisms with the flexibility and robustness to deal with the continuous environmental changes that impose alterations in their genetic programmes during their parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance Replication intitiation sites were defined using two replicates of short nascent strands of increasing sizes (F4 and F5) purified through three rounds of Lambda-exonuclease digestion, and a genomic DNA control (Ctrl). Nucleosome landscape was determined using two replicates of mononucleosomal-DNA derived from MNase-digested chromatin
2016-06-10 | E-GEOD-81991 | biostudies-arrayexpress
Project description:At every cell cycle, faithful inheritance of metazoan genomes requires the concerted activation of thousands of DNA replication origins. However, which genetic and chromatin features define metazoan replication start sites remains largely unknown. Here, we delineate the origin repertoire of the Drosophila genome at high resolution. We address the role of origin-proximal G-quadruplexes and show their ability to transiently stall replication forks in vivo. We dissect the chromatin configuration of replication origins and identify a rich spatial organization of chromatin features at initiation sites. DNA shape and chromatin configurations, not strict sequence specificity, mark and predict replication origins in higher eukaryotes. We further examine the link between transcription and origin firing and reveal that modulation of origin activity across cell types is intimately linked to cell-type-specific transcriptional programs. Our study unravels conserved origin features and provides unique insights into the relationship between DNA topology, chromatin, transcription and replication initiation across metazoa. Our dataset consists of SNS-Seq profiles in Drosophila S2 and Bg3 cells. Small nascent leading strands (SNS) have been purified with an enhanced sensitivity SNS purification protocol. For standard SNS-Seq experiments (from pooled gradient fractions, denoted as "pool"), SNS were purified from two biological replicates. For single-fraction SNS-Seq experiments, two libraries were prepared for each fraction. The genomic coordinates of S2 and Bg3 replication origins are also provided.
2015-04-23 | E-GEOD-65692 | biostudies-arrayexpress
Project description:Mapping origins of replication has been challenging in higher eukaryotes. We have developed a rapid, genome-wide method to map origins in asynchronous human cells by combining the nascent strand abundance assay with a highly-tiled microarray platform, and we validated the technique by two independent assays. We applied this method to analyze the enrichment of nascent DNA in three 50 kb regions containing known origins of replication in the MYC, LMNB2, and HBB genes, a 200 kb region containing the rare fragile site, FRAXA, and a 1075 kb region on chromosome 22, and detected most of the known origins, as well as 28 new origins. Surprisingly, the 28 new origins were small in size, and predominantly located within genes. Our study also revealed a strong correlation between origin replication timing and chromatin acetylation. Keywords: origin mapping, nascent strand DNA, histone acetylaction mapping, ChIP-chip
2007-05-26 | GSE7889 | GEO