H2A.Z Facilitates Licensing and Activation of Early Replication Origins
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ABSTRACT:
PROVIDER: PRJNA557039 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:DNA replication is a tightly regulated process that ensures the precise duplication of the genome during cell cycle. Licensing and activation of eukaryotic replication origins are controlled primarily by chromatin. However, the chromatin features involved and the regulatory mechanism remain largely unknown. In this study, we found that H2A.Z binds Suv420H1 directly to promote H4K20me2 deposition on nucleosome both in vitro and in vivo. ORC1 is subsequently recruited to chromatin for licensing and activation of early replication origins. Depletion of H2A.Z results in defects of DNA replication and cell proliferation in both HeLa cells and T cells. Thus, our results provide novel mechanistic insights that the histone variant H2A.Z epigenetically regulates licensing and activation of the early DNA replication origins through the Suv420H1-H4K20me2-ORC1 pathway.
2019-09-22 | GSE134988 | 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 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:Replication of vertebrate genomes is tightly regulated to ensure accurate duplication, but our understanding of the interplay between genetic and epigenetic factors in this regulation remains incomplete. Here, we investigated the involvement of three elements enriched at gene promoters and replication origins: guanine-rich motifs potentially forming G-quadruplexes (pG4s), nucleosome-free regions (NFRs), and the histone variant H2A.Z, in the firing of origins of replication in vertebrates. We show that two pG4s on the same DNA strand (dimeric pG4s) are sufficient to induce assembly of an efficient minimal replication origin without inducing transcription. Dimeric pG4s in replication origins trigger formation of an NFR next to precisely positioned nucleosomes enriched in H2A.Z on this minimal origin and genome-wide. Thus, our data suggest a crucial role for dimeric pG4s in the organization and duplication of vertebrate genomes. It supports the hypothesis that a nucleosome close to an NFR is a shared signal for the formation of replication origins in eukaryotes.
2023-07-19 | GSE231492 | GEO
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: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:Chromatin structure affects DNA replication patterns, but the role of specific chromatin modifiers in regulating the replication process is yet unclear. We report that phosphorylation of the human SIRT1 deacetylase on Threonine 530 (T530-pSIRT1) modulates DNA synthesis. T530-pSIRT1 associates with replication origins and inhibits replication from a group of ÒdormantÓ potential replication origins, which initiate replication only when cells are subject to replication stress. Although both active and dormant origins bind T530-pSIRT1, active origins are distinguished from dormant origins by their unique association with an open chromatin mark, histone H3 methylated on lysine 4. SIRT1 phosphorylation also facilitates leading and lagging strand coordination. SIRT1 T530 phosphorylation is essential to prevent DNA breakage upon replication stress and cells harboring SIRT1 that cannot be phosphorylated exhibit a high prevalence of extrachromosomal elements, hallmarks of perturbed replication. These observations suggest that SIRT1 phosphorylation modulates the distribution of replication initiation events to insure genomic stability.
2017-06-02 | GSE94403 | 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 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:modENCODE_submission_709 This submission comes from a modENCODE project of David MacAlpine. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: Early origins of replication were identified by treating cells with hydroxyurea (HU), a potent inhibitor of nucleotide synthesis, in the presence of the nucleotide analogue BrdU. Treatment of synchronized Kc167 cells with HU stalls replication forks and activates the intra S-phase checkpoint, thereby limiting BrdU incorporation to those sequences immediately adjacent to early activating replication origins. BrdU enriched sequences surrounding early origins of replication are then enriched by immunoprecipitation with an anti-BrdU antibody. Early origins are then detected by hybridization to Agilent genomic tiling arrays. Peaks are called using MA2C (http://liulab.dfci.harvard.edu/MA2C/MA2C.htm) Keywords: CHIP-chip For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Cell Line: Kc167; Tissue: embryo-derived cell-line; Genotype: se/e; Sex: Female NUMBER OF REPLICATES: 4; EXPERIMENTAL FACTORS: Cell Line Kc167
2010-05-15 | E-GEOD-17285 | biostudies-arrayexpress
Project description:P53 independent P21 expression deregulates replication licensing , leading to genomic instability
2016-05-17 | PXD004140 | Pride
Project description:modENCODE_submission_709 This submission comes from a modENCODE project of David MacAlpine. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: Early origins of replication were identified by treating cells with hydroxyurea (HU), a potent inhibitor of nucleotide synthesis, in the presence of the nucleotide analogue BrdU. Treatment of synchronized Kc167 cells with HU stalls replication forks and activates the intra S-phase checkpoint, thereby limiting BrdU incorporation to those sequences immediately adjacent to early activating replication origins. BrdU enriched sequences surrounding early origins of replication are then enriched by immunoprecipitation with an anti-BrdU antibody. Early origins are then detected by hybridization to Agilent genomic tiling arrays. Peaks are called using MA2C (http://liulab.dfci.harvard.edu/MA2C/MA2C.htm) Keywords: CHIP-chip For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf
2009-07-29 | GSE17285 | GEO