Mapping BRD1 and HBO1 genomic binding in BRCA1 mutant cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE244027 | GEO | 2024/01/11
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of change in transcriptosome after HBO1 knockdown in UWB1.289 ovarian cancer cell line
2019-02-01 | GSE89922 | GEO
Project description:Analysis of change in transcriptosome after stable lentiviral HBO1 knockdown in UWB1.289 ovarian cancer cell line.
2017-12-12 | GSE101972 | GEO
Project description:The regulation of replication forks stalling and replication origins firing must be tightly coordinated to prevents genomic instability. Here we show that GNL3/nucleostemin, a GTP-binding protein able to shuttle between the nucleolus and the nucleoplasm, limits replicative stress by limiting replication origins firing. GNL3 is in proximity of nascent DNA and its depletion reduces forks speed but increases forks density and replication origins firing. When subjected to exogenous replicative stress, cells impaired for GNL3 exhibits MRN-dependent resection and RPA phosphorylation. Strikingly, inhibition of origin firing using CDC7 inhibitor decreased resection in absence of GNL3 but not in absence of BRCA1, suggesting that GNL3 does not protect nascent strand directly from resection. Consistent with this, overexpression of GNL3 leads to an increased resection in response to replicative stress and enhanced origin firing efficiency. These data indicate that the probability of origins firing is tightly regulated by GNL3 to limit replicative stress. Finally, we show that ORC2 and GNL3 interacts together in the nucleolus. We propose a model where GNL3 level is crucial to determine the correct amount of ORC2 on chromatin by sequestrating it in the nucleolus thanks to the capacity of GNL3 to shuttle between nucleoplasm and nucleolus.
2023-07-01 | GSE180865 | GEO
Project description:The origin recognition complex (ORC) marks chromosomal sites as replication origins and is essential for replication initiation. In yeast, ORC also binds to DNA elements called silencers, where its primary function is to recruit silent information regulator (SIR) proteins to establish transcriptional silencing. Indeed, silencers function poorly as chromosomal origins. Several genetic, molecular, and biochemical studies of HMR-E have led to a model proposing that when ORC becomes limiting in the cell, such as in the orc2-1 mutant, only sites that bind ORC tightly, such as HMR-E, remain fully occupied by ORC, while lower affinity sites, including most origins, lose ORC occupancy. Since HMR-E possessed a unique non-replication function, we reasoned that other tight sites might reveal novel functions for ORC on chromosomes. Therefore, we comprehensively determined ORC “affinity” genome-wide by performing an ORC ChIP-on-chip in ORC2 and orc2-1 strains. Here we describe a novel group of orc2-1-resistant ORC-interacting chromosomal sites (ORF-ORC sites) that did not function as replication origins or silencers. Instead, ORF-ORC sites were comprised of protein-coding regions of highly transcribed metabolic genes. In contrast to the ORC-silencer paradigm, transcriptional activation promoted ORC association with these genes. Remarkably, ORF-ORC genes were enriched in proximity to origins of replication, and, in several instances, were transcriptionally regulated by these origins. Taken together, these results suggest a surprising connection between ORC, replication origins and cellular metabolism.
2009-11-07 | GSE18895 | GEO
Project description:Eukaryotic DNA replication initiates from multiple sites on each chromosome called replication origins. In the budding yeast Saccharomyces cerevisiae, origins are defined at discrete sites. Regular spacing and diverse firing characteristics of origins are thought to be required for efficient completion of replication, especially in the presence of replication stress. However, a S. cerevisiae chromosome III harboring multiple origin deletions has been reported to replicate relatively normally, and yet how an origin-deficient chromosome could accomplish successful replication remains unkown. To address this issue, we deleted seven well-characterized origins from chromosome VI, and found that thsese deletions do not cause gross growth defects even in the presence of replication inhibitors. We demonstrated that the origin deletions do cause a strong decrease in the binding of the origin recognition complex. Unexpectedly, replication profiling of this chromosome showed that DNA replication initiates from non-canonical loci around deleted origins in yeast. These results suggest that replication initiation can be unexpectedly flexible in this organism. In this study, we aimed to establish an independent system to investigate how an origin-deficient chromosome is replicated. To this end, we systematically deleted seven well-characterized origins on the left arm of S. cerevisiae chromosome VI and analyzed (1) Orc2 localization during G2/M arrest and (2) BrdU incorporation during synchronous release from G1 arrest into S-phase, and compared the results to wild-type cell signals. For Orc2 ChIP-Chip experiments, Orc-bound DNA was isolated from Orc2-2Xlinker-3XFlag epitope-tagged cells arrested in G2/M using antibodies against Flag. For BrdU ChIP-Chip experiments, actively replicating DNA was isolated from cells harboring a single integrated BrdU incorporation vector released synchronously into 200mM HU using antibodies against BrdU. Immunoprecipitated and input (Orc2) or G1 (BrdU) DNA was then amplified and competitively hybridized to high-resolution strand-specific microarrays covering chromosomes III, VI, and XII.
2014-09-26 | E-GEOD-61743 | biostudies-arrayexpress
Project description:We identified chromatin binding sites for two isforms of BRD1 (BRD1-S and BRD1-L) using ChIP-seq.
2015-10-29 | GSE62811 | GEO
Project description:We identified protein-protein interactions and chromatin binding sites for two isforms of BRD1 (BRD1-S and BRD1-L) using Co-IP MS/MS and ChIP-seq. BRD1 isoforms were cloned, epitope-tagged (pcDNA 6 V5-His6, Lifetechnologies) and stably expressed in HEK293T cells. Chromatin immunoprecipitations were performed using anti V5-antibody conjugated agarose beads (Sigma-Aldrich) and anti HA antibody conjugated agarose beads (Sigma-Aldrich) as controls
2015-10-29 | E-GEOD-62811 | biostudies-arrayexpress
Project description:Background: The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development and susceptibility to schizophrenia and bipolar disorder. Results: To advance the understanding of BRD1 and its role in mental disorders, we characterized the protein and chromatin interactions of the BRD1 isoforms, BRD1-S and BRD1-L, by a series of investigations and integration of functional molecular data with human genetic data. We present several novel protein interactions of BRD1, including proteins previously implicated with mental disorders. By BRD1-S and BRD1-L chromatin immunoprecipitation followed by next generation sequencing we identified binding to promoter regions of 1540 and 823 genes, respectively, and showed correlation between BRD1-S and BRD1-L binding and regulation of gene expression. The identified BRD1 interaction network was found to be predominantly co-expressed with BRD1 mRNA in human brain and enriched for pathways involved in gene expression and brain function. By interrogation of large data sets from genome-wide association studies, we further demonstrate that the BRD1 interaction network is enriched for schizophrenia risk. Conclusion: Our results show that BRD1 interacts with chromatin remodeling proteins, e.g. PBRM1, as well as histone modifiers, e.g. MYST2 and SUV420H1. We find that BRD1 primarily binds in close proximity to transcription start sites and regulates expression of numerous genes, many of which are involved with brain development and susceptibility to mental disorders. Our findings indicate that BRD1 acts as a regulatory hub in a comprehensive schizophrenia risk network which plays a role in many brain regions throughout life, implicating e.g.striatum, hippocampus, and amygdala at mid fetal stages. 9 expression arrays performed in HEK293T cells
2016-03-16 | E-GEOD-79255 | biostudies-arrayexpress
Project description:The origin recognition complex (ORC) binds throughout the genome to initiate DNA replication. In metazoans, it is still unclear how ORC is targeted to specific loci to facilitate helicase loading and replication initiation. Here, we performed immunoprecipitations coupled with mass spectrometry for ORC2 in Drosophila embryos. Surprisingly, we found that ORC2 associates with several subunits of the Nup107-160 subcomplex of the nuclear pore. Bioinformatic analysis revealed that, relative to all modENCODE factors, nucleoporins are among the most enriched factors at ORC2 binding sites. Critically, depletion of the nucleoporin Elys, a member of the Nup107-160 complex, results in decrease ORC2 loading onto chromatin. Depleting Elys also sensitized cells to replication fork stalling, which could reflect a defect in establishing dormant replication origins. Our work reveals a new connection between ORC, replication initiation and nucleoporins, highlighting a previously unrecognized function of nucleoporins in metazoan replication initiation.
2022-10-19 | GSE199896 | GEO
Project description:Background: The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development and susceptibility to schizophrenia and bipolar disorder. Results: To advance the understanding of BRD1 and its role in mental disorders, we characterized the protein and chromatin interactions of the BRD1 isoforms, BRD1-S and BRD1-L, by a series of investigations and integration of functional molecular data with human genetic data. We present several novel protein interactions of BRD1, including proteins previously implicated with mental disorders. By BRD1-S and BRD1-L chromatin immunoprecipitation followed by next generation sequencing we identified binding to promoter regions of 1540 and 823 genes, respectively, and showed correlation between BRD1-S and BRD1-L binding and regulation of gene expression. The identified BRD1 interaction network was found to be predominantly co-expressed with BRD1 mRNA in human brain and enriched for pathways involved in gene expression and brain function. By interrogation of large data sets from genome-wide association studies, we further demonstrate that the BRD1 interaction network is enriched for schizophrenia risk. Conclusion: Our results show that BRD1 interacts with chromatin remodeling proteins, e.g. PBRM1, as well as histone modifiers, e.g. MYST2 and SUV420H1. We find that BRD1 primarily binds in close proximity to transcription start sites and regulates expression of numerous genes, many of which are involved with brain development and susceptibility to mental disorders. Our findings indicate that BRD1 acts as a regulatory hub in a comprehensive schizophrenia risk network which plays a role in many brain regions throughout life, implicating e.g.striatum, hippocampus, and amygdala at mid fetal stages.
2016-03-16 | GSE79255 | GEO