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Comparison of gene expression changes in AML cells after SMARCA4, SMARCD2 or DPF2 knock-down

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE67923 | GEO | 2015/07/12

SECONDARY ACCESSION(S): PRJNA281226

REPOSITORIES: GEO

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Comparison of gene expression changes in AML cells after SMARCA4, SMARCD2 or DPF2 knock-down

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

SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance.

Project description: Not available

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SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells

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

Opposing Role of Dpf2 and Eed on Differentiation of Mouse Embryonic Stem Cells via Regulating Tbx3 (ChIP-seq)

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SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells

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Dpf2 interactome in mouse embryonic stem cells

Project description:Dpf2 is a subunit of the BAF/pBAF chromatin remodelling complex. We have used cross-linking affinity purification-mass spectrometry to explore Dpf2 protein interactions in mouse embryonic stem cells.

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Gene expression changes in MV4-11 cells upon SMARCA4 knock-down and PFI-3 treatment

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