SMARCA4 Rescue Profiling [ChIP]
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ABSTRACT:
PROVIDER: PRJNA547548 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:SMARCA4 Rescue Profiling [RNA]
| PRJNA547549 | ENA
Project description:SMARCA4 Rescue Profiling [Dnase]
| PRJNA547550 | ENA
Project description:Mutations in SMARCA4, a central ATPase of the human BAF/PBAF chromatin remodeling complexes, cause developmental abnormalities and promote cancer development. The pathogenic effects of SMARCA4 loss are often linked to the de-regulation of a relatively small number of key target genes. Here, to understand how chromatin remodeling by SMARCA4 results in specific transcriptional perturbations, we used genome engineering to correct a homozygous mutation in SMARCA4 in the well-characterized lung adenocarcinoma A549 cell line and profiled changes in SMARCA2/4 occupancy, chromatin accessibility, histone marks and transcription. Restoration of SMARCA4 causes a dramatic increase in chromatin accessibility at low affinity TF binding sites. Despite the widespread increase in chromatin accessibility, we observe comparatively attenuated changes in gene expression. Although there is a marked correlation between the number of local activated DHSs and the transcriptional responsivity of a gene, the influence of distal DHSs appears modified by a gene's promoter architecture and domain-scale chromatin organization. The largest changes in expression occur for genes in isolated, SMARCA4 sensitive chromatin domains that undergo region-wide chromatin remodeling upon reintroduction of SMARCA4. Our results reveal that interactions between distal enhancers, genome organization, and promoter architecture add transcriptional specificity to the global chromatin effects of BAF/PBAF complex perturbation and target the response to key developmental pathways.
2020-05-20 | GSE132290 | GEO
Project description:Mutations in SMARCA4, a central ATPase of the human BAF/PBAF chromatin remodeling complexes, cause developmental abnormalities and promote cancer development. The pathogenic effects of SMARCA4 loss are often linked to the de-regulation of a relatively small number of key target genes. Here, to understand how chromatin remodeling by SMARCA4 results in specific transcriptional perturbations, we used genome engineering to correct a homozygous mutation in SMARCA4 in the well-characterized lung adenocarcinoma A549 cell line and profiled changes in SMARCA2/4 occupancy, chromatin accessibility, histone marks and transcription. Restoration of SMARCA4 causes a dramatic increase in chromatin accessibility at low affinity TF binding sites. Despite the widespread increase in chromatin accessibility, we observe comparatively attenuated changes in gene expression. Although there is a marked correlation between the number of local activated DHSs and the transcriptional responsivity of a gene, the influence of distal DHSs appears modified by a gene's promoter architecture and domain-scale chromatin organization. The largest changes in expression occur for genes in isolated, SMARCA4 sensitive chromatin domains that undergo region-wide chromatin remodeling upon reintroduction of SMARCA4. Our results reveal that interactions between distal enhancers, genome organization, and promoter architecture add transcriptional specificity to the global chromatin effects of BAF/PBAF complex perturbation and target the response to key developmental pathways.
2020-05-20 | GSE132292 | GEO
Project description:Mutations in SMARCA4, a central ATPase of the human BAF/PBAF chromatin remodeling complexes, cause developmental abnormalities and promote cancer development. The pathogenic effects of SMARCA4 loss are often linked to the de-regulation of a relatively small number of key target genes. Here, to understand how chromatin remodeling by SMARCA4 results in specific transcriptional perturbations, we used genome engineering to correct a homozygous mutation in SMARCA4 in the well-characterized lung adenocarcinoma A549 cell line and profiled changes in SMARCA2/4 occupancy, chromatin accessibility, histone marks and transcription. Restoration of SMARCA4 causes a dramatic increase in chromatin accessibility at low affinity TF binding sites. Despite the widespread increase in chromatin accessibility, we observe comparatively attenuated changes in gene expression. Although there is a marked correlation between the number of local activated DHSs and the transcriptional responsivity of a gene, the influence of distal DHSs appears modified by a gene's promoter architecture and domain-scale chromatin organization. The largest changes in expression occur for genes in isolated, SMARCA4 sensitive chromatin domains that undergo region-wide chromatin remodeling upon reintroduction of SMARCA4. Our results reveal that interactions between distal enhancers, genome organization, and promoter architecture add transcriptional specificity to the global chromatin effects of BAF/PBAF complex perturbation and target the response to key developmental pathways.
2020-05-20 | GSE132291 | GEO
Project description:To reveal the genome-wide targets of SWI/SNF complexes in neuroblastoma cells, we performed ChIP-seq of SMARCA4 (BRG1) in IMR-32, KELLY, and SK-N-DZ cells. We used these libraries to examine chromatin occupancy profiling. Analysis of locations reveal that SMARCA4 targets directly regulate sites regulated by the neuroblastoma core regulatory circuitry.
2023-10-24 | GSE190707 | GEO
Project description:SMARCA2 and SMARCA4 are two mutually exclusive ATPase subunits of SWI/SNF complex. SMARCA4 deficient lung cancer population selectively depend on SMARCA2 for cancer growth phenotype. Rescue experiments with ectopic expression of wild-type, bromodomain mutant and ATPase dead SMARCA2 and SMARCA4 highlight that ATPase domain is the drug target. In this study, we performed genome-wide microarray and differential gene expression profiling on isogenic lung cancer lines expressing cDNA rescue constructs for wild-type, bromodomain mutant and ATPase dead SMARCA2 and SMARCA4
2015-07-21 | GSE69088 | GEO
Project description:To study the genome-wide effects of wild type and mutant SMARCA4 and of SAHA on the dynamics of H3K27 modification, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) of SMARCA4, EZH2, H3K27ac and H3K27me3, in the H1299 cell model
2021-05-28 | GSE155129 | GEO
Project description:Using ChIP-seq, we identified the genome-wide occupancy of SMARCA2 and SMARCA4 in lung cancer cells (NCI-H1944) reconstituted with SMARCA4 WT. We also determined how SMARCA4 occupancy changed in NCI-H1944 after SMARCA2 depletion.
2020-09-10 | GSE147201 | GEO