Expression changes following conditional deletion of SMARCA4 (Brg) in mouse embryonic stem cells [RNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE88967 | GEO | 2016/10/21
SECONDARY ACCESSION(S): PRJNA349263
REPOSITORIES: GEO
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Project description:Pharmacological inhibition of the SMARCA4 bromodomain inhibited human leukemic cell proliferation, phenocopying SMARCA4 knockdown in these cells. We performed microarray analysis of global gene expression changes in MV4-11 cells after 6 days of PFI-3 treatment and after SMARCA4 knock-down. With this analysis we identified several genes whose expression was similarly up- or down-regulated upon inhibitor treatment and SMARCA4 depletion. Human acute monocytic leukemia cells (MV4-11, ACC 102) were lentivirally transduced with shRNA taregting SMARCA4 (KD) or with a negative control shRNA (Scr). In a parallel experiment MV4-11 cells were treated for 6 days with 10 uM PFI-3, which is SMARCA4, SMARCA2 and PBRM1 bromodomain inhibitor, or DMSO as a negative control. All sample types were prepared in triplicates.
2015-07-12 | E-GEOD-67920 | biostudies-arrayexpress
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:The packaging of DNA into chromatin plays an important role in transcriptional regulation and nuclear processes. Brahma related gene-1 SMARCA4 (also known as BRG1), the essential ATPase subunit of the mammalian SWI/SNF chromatin remodeling complex, uses the energy from ATP hydrolysis to disrupt nucleosomes at target regions. Although the transcriptional role of SMARCA4 at gene promoters is well-studied, less is known about its role in higher-order genome organization. SMARCA4 knockdown in human mammary epithelial MCF-10A cells resulted in 176 up-regulated genes, including many related to lipid and calcium metabolism, and 1292 down-regulated genes, some of which encode extracellular matrix (ECM) components that can exert mechanical forces and affect nuclear structure. ChIP-seq analysis of SMARCA4 localization and SMARCA4-bound super-enhancers demonstrated extensive binding at intergenic regions. Furthermore, Hi-C analysis showed extensive SMARCA4-mediated alterations in higher-order genome organization at multiple resolutions. First, SMARCA4 knockdown resulted in clustering of intra- and inter- sub-telomeric regions, demonstrating a novel role for SMARCA4 in telomere organization. SMARCA4 binding was enriched at TAD (Topologically Associating Domain) boundaries, and SMARCA4 knockdown resulted in weakening of TAD boundary strength. Taken together, these findings provide a dynamic view of SMARCA4-dependent changes in higher-order chromatin organization and gene expression, identifying SMARCA4 as a novel component of chromatin organization. Hi-C and RNA-seq experiments were conducted in MCF-10A shSCRAM and shSMARCA4 cells. SMARCA4 ChIP-seq was conducted in wildtype MCF-10A cells.
2016-06-02 | E-GEOD-74716 | biostudies-arrayexpress
Project description:Spinal cord mRNA profiles of 14-day-old control (Brg1c/+;Olig1-Cre) and Smarca4/Brg1 conditional knockout (Brg1c/c;Olig1-Cre) mice were generated by RNA-seq. Differential expressed genes are identified using Cuffdiff and validated with qPCR. Spinal cord mRNA profiles of 14-day old control and Brg1c/c;Olig1-Cre mice were generated by RNA-sequencing.
2013-01-20 | E-GEOD-42443 | biostudies-arrayexpress
Project description:Purpose: The purpose of this study was to develop a framework for analyzing RPE expression profiles from zebrafish eye mutants. Methods: The fish model we used was smarca4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4), a retinal dystrophic mutant that the retinal phenotype and expression profiles were previously characterized. Histological and Affymetrix GeneChip analyses were conducted to define the RPE defects and underlying differential expression respectively. Results: Histological analysis indicates that smarca4 RPE was formed but its differentiation was abnormal. In particular, ultra-structural analysis of smarca4 RPE by transmission electron microscopy showed a number of defects in melanogenesis, suggesting that the cytoskeletal dynamics was impaired. To compare the expression profile of normal wild-type (WT) and smarca4 RPE, their retinas and RPE-attached retinas were microdissected and the gene expression values of these tissues measured by Affymetrix GeneChip analysis. The RPE expression values were then estimated from these samples using an approach previously established by us. A factorial analysis was conducted using the expression values of RPE, retinal as well as the whole-embryo samples. Specific rules (contrasts) were built using the coefficients of the resulting fitted model to select for three groups of genes: 1) Smarca4-regulated RPE genes, 2) Smarca4-regulated retinal genes, and 3) Smarca4-regulated RPE genes that are not differentially expressed in the retina. The latter group consists of 39 genes that are highly related to cytoskeletal dynamics, melanogenesis, paracrine and intracellular signal transduction. Conclusions: Our analytical framework can potentially identify genes in zebrafish mutants that both retina and RPE are affected by the underlying mutation. The gene expression levels of three independent replicates of WT whole embryos (WA52), WT retinas (WR52), WT RPE-attached retinas (WRR52), smarca4/yng retinas (YR52), smarca4 RPE-attached retinas (YRR52) and smarca4 whole embryos (YA52) were measured by Affymetrix Zebrafish Whole Genome Arrays. All samples were collected at 52 hpf. The probe-level data of these sample groups were background adjusted, normalized and summarized by a robust multiarray average (RMA) algorithm. RPE expression values were estimated from the comparison between the retinal and RPE-attached retinal samples of the same genotype based on a method we previously developed (Leung et al., Invest Ophthalmol Vis Sci. 2007; 48:881). Then, a 3x2 factorial design was used to analyze the expression values of three kinds of tissue (T): whole embryo, retina and RPE in two kinds of mutation (M) background: WT and smarca4. Using the coefficients from the fitted models, contrasts were built to identify candidate genes that fulfilled specific criteria. The false discovery rate (FDR) q-value cutoff for a contrast was 0.001. Several contrasts were ultimately combined to allow for selection of genes that were regulated by Smarca4 in the retina and RPE. These include 1) Smarca4-regulated RPE genes, 2) Smarca4-regulated retinal genes, and 3) Smarca4-regulated RPE genes that are not differentially expressed in the retina.
2014-01-03 | E-GEOD-50241 | biostudies-arrayexpress
Project description:We investigated transcriptomic effects of a Smarca4 ATPase mutant observed in primary tumors and cancer cell lines. Heterozygous expression of G784E Smarca4 mutant led to transcriptional changes compared to cells expressing only wild-type Smarca4.
2017-10-22 | GSE98469 | GEO
Project description:Pharmacological inhibition of the SMARCA4 bromodomain inhibited human leukemic cell proliferation, phenocopying SMARCA4 knockdown in these cells. We performed microarray analysis of global gene expression changes in MV4-11 cells after 6 days of PFI-3 treatment and after SMARCA4 knock-down. With this analysis we identified several genes whose expression was similarly up- or down-regulated upon inhibitor treatment and SMARCA4 depletion.
2015-07-12 | GSE67920 | GEO
Project description:We explored the role of SMARCA4 and the two Brahma associated factors SMARCD2 and DPF2 in leukaemia. We observed the selective requirement for these factors for leukemic cell expansion, as well as extended survival of mice transplanted with leukaemic cells with reduced expression of these genes. Gene expression profiling revealed largely similar alterations with the down-regulation of each of these three factors, suggesting a concerted function in transformed blood cells. These changes included loss of pluripotency-associated signature but did not correlate with c-MYC down-regulation. Human acute monocytic leukemia cells (THP-1, ACC 16) were lentivirally transduced with pLKO-puro vectors carrying shRNAs against SMARCA4, SMARCD2 or DPF2. As a negative control, THP-1 cells were transduced with pLKO-puro-shScr (Scrambled). All samples were prepared as biological triplicates.
2015-07-12 | E-GEOD-67923 | biostudies-arrayexpress
Project description:We performed a conditional ablation of Wt1 in the myocardium of mice embryos. RNASeq analysis identified differential expression of 137 genes in the E13.5 mutant heart as compared to controls. GO functional enrichment analysis suggested that both calcium ion regulation and modulation of potassium channels are deeply altered in the mutant myocardium
2021-07-10 | GSE178220 | GEO