Genomic occupancy of the INO80 complex [II]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107730 | GEO | 2018/01/23
REPOSITORIES: GEO
Similar Datasets
Project description:We mapped 4 subunits of the INO80 complex using ChIP-seq in HepG2 and Huh7 liver cancer cell lines. We found a subclass of sites occupied by the INO80 ATPase subunit, but not by any accessory subunits that we call 'Autonomous' INO80 sites. These sites are present in both HepG2 and Huh7 cells and are characterized by repressed chromatin. Relief of reprissive histone modifications thorugh EZH2 inhbiition led to the increase in H3K27ac at INO80 targets.
2020-04-01 | GSE97411 | GEO
Project description:In the multi-subunit INO80 chromatin-remodeling complex, all the auxiliary subunits assemble on three distinct domains of the catalytic chromatin remodeler INO80, which are N-terminal domain, HSA domain, and ATPase domain. While the ATPase and HSA domains and the auxiliary subunits assembling on the domains are known to be responsible for ATP hydrolysis and chromatin remodeling, it is largely unknown how the auxiliary subunits assembling on the INO80 N-terminal domain regulate the chromatin status. We identify both conserved and non-conserved auxiliary subunits of the INO80 complex in Arabidopsis thaliana. All the auxiliary subunits assemble on the conserved N-terminal domain, HSA domain, and ATPase domain of INO80 in Arabidopsis. While the auxiliary subunits assembling on the INO80 ATPase domain are required for the ATPase-dependent function, the INO80 N-terminal domain and the auxiliary subunits assembling on the domain can regulate gene expression and development even when the ATPase domain is absent, suggesting that INO80 has an ATPase-independent role. Furthermore, we find that a subclass of the COMPASS histone H3K4 methyltransferase complexes assemble on the INO80 N-terminal domain in the INO80 complex and function together with the other auxiliary subunits assembling on the INO80 N-terminal domain, thereby facilitating the ATPase-independent function. This study suggests that the conserved chromatin remodeler INO80 has an ATPase-independent role and demonstrates that the auxiliary subunits assembling on the INO80 N-terminal domain are required for the ATPase-independent role.
2021-05-25 | GSE162373 | GEO
Project description:In the multi-subunit INO80 chromatin-remodeling complex, all the auxiliary subunits assemble on three distinct domains of the catalytic chromatin remodeler INO80, which are N-terminal domain, HSA domain, and ATPase domain. While the ATPase and HSA domains and the auxiliary subunits assembling on the domains are known to be responsible for ATP hydrolysis and chromatin remodeling, it is largely unknown how the auxiliary subunits assembling on the INO80 N-terminal domain regulate the chromatin status. We identify both conserved and non-conserved auxiliary subunits of the INO80 complex in Arabidopsis thaliana. All the auxiliary subunits assemble on the conserved N-terminal domain, HSA domain, and ATPase domain of INO80 in Arabidopsis. While the auxiliary subunits assembling on the INO80 ATPase domain are required for the ATPase-dependent function, the INO80 N-terminal domain and the auxiliary subunits assembling on the domain can regulate gene expression and development even when the ATPase domain is absent, suggesting that INO80 has an ATPase-independent role. Furthermore, we find that a subclass of the COMPASS histone H3K4 methyltransferase complexes assemble on the INO80 N-terminal domain in the INO80 complex and function together with the other auxiliary subunits assembling on the INO80 N-terminal domain, thereby facilitating the ATPase-independent function. This study suggests that the conserved chromatin remodeler INO80 has an ATPase-independent role and demonstrates that the auxiliary subunits assembling on the INO80 N-terminal domain are required for the ATPase-independent role.
2021-05-25 | GSE162374 | GEO
Project description:INO80 complex is an ATPase-dependent chormatin remodeling complex, which regulates various DNA metabolic processes such as DNA replication and repair. Additionally, INO80 complex also contributes to the regulation of gene expression in sterss response and development. In order to investigate the function of INO80 complex in rhabdomyosarcoma, we examined the knockdown of subunits of INO80 complex Actr5, Ies6, and Ino80 in human rhabdomyosarcoma RD cells. As a result, it was found that INO80 complex is involved in the sarcomagenicity and the disregulation of myogenic properties of rhabdomyosarcoma cells.
2022-04-01 | GSE169681 | GEO
Project description:Background: Chromatin remodeling complexes facilitate the access of enzymes that mediate transcription, replication or repair of DNA by modulating nucleosome position and/or composition. Ino80 is the DNA-dependent Snf2-like ATPase subunit of a complex whose nucleosome remodeling activity requires actin-related proteins, Arp4, Arp5 and Arp8, as well as two RuvB-like DNA helicase subunits. Budding yeast mutants deficient for Ino80 function are not only hypersensitive to reagents that induce DNA double strand breaks, but also to those that impair replication fork progression. Results: To understand why ino80 mutants are sensitive to agents that perturb DNA replication, we used chromatin immunoprecipitation to map the binding sites of the Ino80 chromatin remodeling complex on four budding yeast chromosomes. We found that Ino80 and Arp5 binding sites coincide with origins of DNA replication and tRNA genes. In addition, Ino80 was bound at 67% of the promoters of genes that are sensitive to ino80 mutation. When replication forks were arrested near origins in the presence of hydroxyurea (HU), the presence of the Ino80 complex at stalled forks and at unfired origins increased dramatically. Importantly, the resumption of DNA replication after release from a HU block was impaired in the absence of Ino80 activity. Mutant cells accumulated double-strand breaks as they attempted to restart replication. Consistently, ino80-deficient cells, although proficient for checkpoint activation, delay recovery from the checkpoint response. Conclusions: The Ino80 chromatin remodeling complex is enriched at stalled replication forks where it promotes the resumption of replication upon recovery from fork arrest. Keywords: ChIP-chip • The goal of the experiment Genome-wide localization of Ino80 on chromosome in Saccharomyces cerevisiae • Keywords DNA replication, Saccharomyces cerevisiae, Genome tilling array (chromosome III, IV, V, VI) • Experimental factor Distribution of Ino80 in random culture Distribution of Ino80 in G1 phase Distribution of Ino80 in early S phase • Experimental design ChIP analyses: W303 background cells expressing Myc-tagged Ino80 were used for the ChIP using anti-Myc monoclonal antibody (9E11). ChIP-chip analyses: In all cases, hybridization data for ChIP fraction was compared with WCE (whole cell extract) fraction. Saccharomyces cerevisiae affymetrix genome tiling array (SC3456a520015F for chromosome III, IV, V, VI) was used. • Quality control steps taken Confirmation of several loci by quantitative real time PCR.
2008-04-10 | E-GEOD-9420 | biostudies-arrayexpress
Project description:Background: Chromatin remodeling complexes facilitate the access of enzymes that mediate transcription, replication or repair of DNA by modulating nucleosome position and/or composition. Ino80 is the DNA-dependent Snf2-like ATPase subunit of a complex whose nucleosome remodeling activity requires actin-related proteins, Arp4, Arp5 and Arp8, as well as two RuvB-like DNA helicase subunits. Budding yeast mutants deficient for Ino80 function are not only hypersensitive to reagents that induce DNA double strand breaks, but also to those that impair replication fork progression. Results: To understand why ino80 mutants are sensitive to agents that perturb DNA replication, we used chromatin immunoprecipitation to map the binding sites of the Ino80 chromatin remodeling complex on four budding yeast chromosomes. We found that Ino80 and Arp5 binding sites coincide with origins of DNA replication and tRNA genes. In addition, Ino80 was bound at 67% of the promoters of genes that are sensitive to ino80 mutation. When replication forks were arrested near origins in the presence of hydroxyurea (HU), the presence of the Ino80 complex at stalled forks and at unfired origins increased dramatically. Importantly, the resumption of DNA replication after release from a HU block was impaired in the absence of Ino80 activity. Mutant cells accumulated double-strand breaks as they attempted to restart replication. Consistently, ino80-deficient cells, although proficient for checkpoint activation, delay recovery from the checkpoint response. Conclusions: The Ino80 chromatin remodeling complex is enriched at stalled replication forks where it promotes the resumption of replication upon recovery from fork arrest. Keywords: ChIP-chip • The goal of the experiment Genome-wide localization of Ino80 and Arp5 on chromosome in Saccharomyces cerevisiae • Keywords DNA replication, Saccharomyces cerevisiae, Genome tilling array (chromosome III, IV, V, VI) • Experimental factor Distribution of Ino80 and Arp5 in wild type in random culture Distribution of Ino80 in G1 cells Distribution of Ino80 in early S phase cells • Experimental design ChIP analyses: W303 background cells expressing Myc tagged Ino80 were used for the ChIP using anti-Myc monoclonal antibody (9E11). ChIP analyses: W303 background cells expressing Myc tagged Ino80 were used for the ChIP using anti-Arp5 polyclonal antibody. ChIP-chip analyses: In all cases, hybridization data for ChIP fraction was compared with WCE (whole cell extract) fraction. Saccharomyces cerevisiae affymetrix genome tiling array (SC3456a520015F for chromosome III, IV, V, VI) was used. • Quality control steps taken Confirmation of several loci by quantitative real time PCR.
2008-04-10 | E-GEOD-9233 | biostudies-arrayexpress
Project description:Background: Chromatin remodeling complexes facilitate the access of enzymes that mediate transcription, replication or repair of DNA by modulating nucleosome position and/or composition. Ino80 is the DNA-dependent Snf2-like ATPase subunit of a complex whose nucleosome remodeling activity requires actin-related proteins, Arp4, Arp5 and Arp8, as well as two RuvB-like DNA helicase subunits. Budding yeast mutants deficient for Ino80 function are not only hypersensitive to reagents that induce DNA double strand breaks, but also to those that impair replication fork progression. Results: To understand why ino80 mutants are sensitive to agents that perturb DNA replication, we used chromatin immunoprecipitation to map the binding sites of the Ino80 chromatin remodeling complex on four budding yeast chromosomes. We found that Ino80 and Arp5 binding sites coincide with origins of DNA replication and tRNA genes. In addition, Ino80 was bound at 67% of the promoters of genes that are sensitive to ino80 mutation. When replication forks were arrested near origins in the presence of hydroxyurea (HU), the presence of the Ino80 complex at stalled forks and at unfired origins increased dramatically. Importantly, the resumption of DNA replication after release from a HU block was impaired in the absence of Ino80 activity. Mutant cells accumulated double-strand breaks as they attempted to restart replication. Consistently, ino80-deficient cells, although proficient for checkpoint activation, delay recovery from the checkpoint response. Conclusions: The Ino80 chromatin remodeling complex is enriched at stalled replication forks where it promotes the resumption of replication upon recovery from fork arrest. Keywords: ChIP-chip
2008-04-10 | GSE9420 | GEO
Project description:Background: Chromatin remodeling complexes facilitate the access of enzymes that mediate transcription, replication or repair of DNA by modulating nucleosome position and/or composition. Ino80 is the DNA-dependent Snf2-like ATPase subunit of a complex whose nucleosome remodeling activity requires actin-related proteins, Arp4, Arp5 and Arp8, as well as two RuvB-like DNA helicase subunits. Budding yeast mutants deficient for Ino80 function are not only hypersensitive to reagents that induce DNA double strand breaks, but also to those that impair replication fork progression. Results: To understand why ino80 mutants are sensitive to agents that perturb DNA replication, we used chromatin immunoprecipitation to map the binding sites of the Ino80 chromatin remodeling complex on four budding yeast chromosomes. We found that Ino80 and Arp5 binding sites coincide with origins of DNA replication and tRNA genes. In addition, Ino80 was bound at 67% of the promoters of genes that are sensitive to ino80 mutation. When replication forks were arrested near origins in the presence of hydroxyurea (HU), the presence of the Ino80 complex at stalled forks and at unfired origins increased dramatically. Importantly, the resumption of DNA replication after release from a HU block was impaired in the absence of Ino80 activity. Mutant cells accumulated double-strand breaks as they attempted to restart replication. Consistently, ino80-deficient cells, although proficient for checkpoint activation, delay recovery from the checkpoint response. Conclusions: The Ino80 chromatin remodeling complex is enriched at stalled replication forks where it promotes the resumption of replication upon recovery from fork arrest. Keywords: ChIP-chip
2008-04-10 | GSE9233 | GEO
Project description:Super-enhancers (SEs) are large genomic regions with high density of enhancer marks. In cancer, SEs are found near oncogenes and dictate cancer gene expression. However, how oncogenic SEs are regulated remains poorly understood. Here, we show that INO80, a chromatin remodeling complex, is required for SE-mediated oncogenic transcription and tumor growth in melanoma. The expression of Ino80, the SWI/SNF ATPase, is elevated in melanoma cells and patient melanomas compared to normal melanocytes and benign nevi. Furthermore, Ino80 silencing selectively inhibits melanoma cell proliferation, anchorage-independent growth, as well as tumorigenesis and tumor maintenance in mouse xenografts. Mechanistically, Ino80 occupies more than 90% of SEs, and its occupancy is dependent on transcription factors such as MITF and Sox9. Ino80 binding reduces nucleosome occupancy and facilitates Mediator recruitment, thus promoting oncogenic transcription. Consistently, genes co-occupied by Ino80 and Med1 are specifically expressed in melanomas compared to melanocytes. Together, our results reveal an essential role of INO80-dependent chromatin remodeling in SE function, and suggest a novel strategy for disrupting SEs in cancer treatment. Human melanoma cell line A375 cells were infected with shNT or shIno80, and total RNA was extracted 2, 3, 4 days after infection. The RNA was submitted to RNA-Seq subsequently. For ChIP-Seq, either wild type A375 and SK-MEL-147, or A375 infected with shNT or shIno80, was used for ChIP-Seq for corresponding factors.
2016-07-07 | E-GEOD-82333 | biostudies-arrayexpress
Project description:Super-enhancers (SEs) are large genomic regions with high density of enhancer marks. In cancer, SEs are found near oncogenes and dictate cancer gene expression. However, how oncogenic SEs are regulated remains poorly understood. Here, we show that INO80, a chromatin remodeling complex, is required for SE-mediated oncogenic transcription and tumor growth in melanoma. The expression of Ino80, the SWI/SNF ATPase, is elevated in melanoma cells and patient melanomas compared to normal melanocytes and benign nevi. Furthermore, Ino80 silencing selectively inhibits melanoma cell proliferation, anchorage-independent growth, as well as tumorigenesis and tumor maintenance in mouse xenografts. Mechanistically, Ino80 occupies more than 90% of SEs, and its occupancy is dependent on transcription factors such as MITF and Sox9. Ino80 binding reduces nucleosome occupancy and facilitates Mediator recruitment, thus promoting oncogenic transcription. Consistently, genes co-occupied by Ino80 and Med1 are specifically expressed in melanomas compared to melanocytes. Together, our results reveal an essential role of INO80-dependent chromatin remodeling in SE function, and suggest a novel strategy for disrupting SEs in cancer treatment. Human melanoma cell line A375 cells were infected with shNT or shIno80, and total RNA was extracted 2, 3, 4 days after infection. The RNA was submitted to RNA-Seq subsequently. For ChIP-Seq, either wild type A375 and SK-MEL-147, or A375 infected with shNT or shIno80, was used for ChIP-Seq for corresponding factors.
2016-07-07 | E-GEOD-82330 | biostudies-arrayexpress