H2A.Z Facilitates Licensing and Activation of Early Replication Origins
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE134988 | GEO | 2019/09/22
REPOSITORIES: GEO
Similar Datasets
Project description:DNA replication ensures the accurate transmission of genetic information during cell cycle. The interaction between histone methyltransferase SUV420H1 and histone variant H2A.Z plays a critical role in the licensing of early replication origins. However, the mechanism by which SUV420H1 preferentially recognizes H2A.Z-nucleosome and deposits H4 lysine 20 dimethylation (H4K20me2) on DNA replication origins remains elusive. Here, we determined the cryo-EM structures of SUV420H1 bound to H2A.Z-nucleosome or H2A-nucleosome. Our structures show that the SUV420H1 catalytic domain (CD) directly interacts with histone H4 and nucleosomal DNA, whereas a SUV420H1 arginine-rich motif (ARM) anchors to the acidic patch of the nucleosome. The N-terminal aminal acid residues of H4 (Aa 1-24) forms a lasso-shaped structure sandwiched between SUV420H1 CD and nucleosome. The lasso-shaped structure stabilizes the SUV420H1-nucleosome interaction and precisely projects the H4 K20 residue into the SUV420H1 catalytic center. Further analyses revealed a crucial role of SUV420H1 KR-loop (aminal acid residues 214-223), which spatially lies closely to H2A.Z specific residues D97/S98, in dictating the preference for H2A.Z-nucleosome. SUV420H1 K219A/R220A mutations reduced the activity of SUV420H1 for H4K20me2 modification, the preference of SUV420H1 for H2A.Z-nucleosome, and the efficiency of DNA replication initiation. Collectively, our findings elucidate how SUV420H1 preferentially recognizes H2A.Z-nucleosome to deposit H4K20me2 modification and shed light on therapeutic strategies targeting the DNA replication initiation.
2023-12-04 | GSE210197 | GEO
Project description:H2A.Z Facilitates Licensing and Activation of Early Replication Origins
| PRJNA557039 | ENA
Project description:The role of histone modifications in DNA replication remains poorly understood. Here, we show that histone H4K20 monomethylation (me1) favors the assembly of the pre-replication complex on chromatin, an association that is increased when H4K20me1 is converted to trimethylation (H4K20me3). Remarkably, these histone methylations enhance origin activity, indicating a positive role in both origin licensing and activation. Genome-wide approaches revealed that H4K20me1 and H4K20me3 are enriched in distinct GC-rich regions, where their presence correlates with early-replicating and late-firing origins respectively. Accordingly, depletion of H4K20me1 at early origins delays the replication of active chromatin. Conversely, loss of H4K20me2/3 causes a drop in the licensing and activity of late-firing origins, slowing down the replication of heterochromatin. Altogether, these results suggest that the concerted activity of mammalian H4K20 methyltransferases and the resulting distribution of H4K20me states are essential to ensure the order and replication timing of different chromatin states.
2017-05-31 | GSE82065 | 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. 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. As part of a project for profiling replication origins in Arabidopsis thaliana, we have performed ChIP-chip analysis of the binding of ORC1 and CDC6, two proteins involved in initiation of DNA replication. Here, we provide the data of the ORC1-bound and CDC6-bound genomic sites using as control genomic DNA.
2011-02-06 | GSE21928 | GEO
Project description:The budding yeast genome is marked by 250-350 origins of DNA replication. These origins are bound by the origin recognition complex (ORC) throughout the cell cycle. ORC has known DNA binding sequence preferences which, though necessary for binding, are not sufficient to fully specify a genomic locus as being bound by ORC, indicating that the cell must use additional chromosomal cues to specify ORC binding sites and origins of replication. Using high-throughput sequencing to precisely locate both ORC binding sites and nucleosome locations genome-wide, we find that a nucleosome depleted region (NDR) and precisely positioned nucleosomes are a ubiquitous feature of yeast replication origins. The ARS consensus sequence (ACS) and adjacent sequences are sufficient to maintain the nucleosome-free properties of the NDR. We use a temperature sensitive ORC1 mutant to demonstrate that ORC is required to maintain precisely positioned nucleosomes at origins of replication. These findings demonstrate the importance of local nucleosome positioning at replication origins, and that chromatin organization is an important determinant of origin selection. Examination of nucleosome positioning in wild-type and orc1-161ts mutant S. cerevisiae at room temperature and heatshock temperatures. Examination of ORC binding locations by ChIP-seq. All reported coordinates are based on the SGD genome build released 12/16/2005.
2010-03-19 | E-GEOD-16926 | biostudies-arrayexpress
Project description:Recent advances in the study of archaeal DNA replication have uncovered defined replication origins (oriC) and demonstrated specific binding of the Cdc6/Orc1 protein and Mcm helicase to oriC in vivo and/or in vitro. The oriC of the hyperthermophilic archaeon Pyrococcus abyssi is characterized by 13 bp repeats, AT-rich regions and an inverted repeat whose precise roles remain unclear. We report here that the 13 bp repeats are widespread in the three Pyrococcus genomes. Nevertheless, by means of chromatin immunoprecipitation coupled with hybridization on a whole genome microarray (ChIP-chip), we found that binding of P. abyssi Cdc6/Orc1 to oriC in vivo was highly specific both in exponential and stationary phases, allowing oriC to be distinguished in the 1.8 M bp genome. ChIP-chip analysis also indicated that a single 13 bp repeat is not sufficient for stable binding of Cdc6/Orc1. Purified Cdc6/Orc1 binds a DNA fragment containing the inverted repeat of oriC with a relatively low affinity, suggesting that multiple clusters of the 13 bp repeat discovered in this study contribute to the stable binding of Cdc6/Orc1 to oriC. Our ChIP-chip analysis revealed that Mcm also binds oriC only in proliferating cells, consistent with its role as a licensing factor. Finally, we found that both Cdc6/Orc1 and Mcm have one additional target site. Notably, Mcm binds constitutively to a GC-rich region containing two rRNA genes and a tRNA gene, suggesting a role of archaeal Mcm in DNA replication and/or transcription of this peculiar region. Keywords: ChIP-chip
2008-01-01 | GSE4104 | 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 | GSE21827 | GEO