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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human NCI-H522

ABSTRACT: The transcription factors Smad2 and Smad3 mediate a large set of genes responses induced by the cytokine TGFÎ², but the extent to which their function depends on chromatin remodeling remains to be defined. We observed interactions between these two Smads and BRG1, BAF250b, BAF170 and BAF155, which are core components of the SWI/SNF chromatin-remodeling complex. Smad2 and Smad3 have a similar affinity for these components in vitro, and their interactions are primarily mediated by BRG1. In vivo, however, BRG1 predominantly interacts with Smad3, and this interaction is enhanced by TGFÎ² stimulation. Our results suggest that BRG1 is incorporated into transcriptional complexes that are formed by activated Smads in the nucleus, on target promoters. Using BRG1-deficient cell systems(H522 lung cancer cells), we defined the BRG1 dependence of the TGFÎ² transcriptional program genome-wide. Most TGFÎ² gene responses in human epithelial cells are dependent on BRG1 function. Remarkably, BRG1 is not required for the TGFÎ²-mediated induction of SMAD7 and SNON, which encode key mediators of negative feedback in this pathway. Our results provide a genome-wide scope of the participation of BRG1 in TGFÎ² action and suggest a widespread yet differential involvement of BRG1 SWI/SNF remodeler in the transcriptional response of many genes to this cytokine. Experiment Overall Design: NCI-H522 cells that were transduced with BRG1, TÎ²R-II, or both vectors combined were incubated with TGFÎ² and subjected to transcriptomic analysis. Totally 6 samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Qiaoran Xi

PROVIDER: E-GEOD-10847 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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H522 lung cancer cells' TGFbeta response was restored by putting back BRG1 and TGFbRII

Project description:The transcription factors Smad2 and Smad3 mediate a large set of genes responses induced by the cytokine TGFβ, but the extent to which their function depends on chromatin remodeling remains to be defined. We observed interactions between these two Smads and BRG1, BAF250b, BAF170 and BAF155, which are core components of the SWI/SNF chromatin-remodeling complex. Smad2 and Smad3 have a similar affinity for these components in vitro, and their interactions are primarily mediated by BRG1. In vivo, however, BRG1 predominantly interacts with Smad3, and this interaction is enhanced by TGFβ stimulation. Our results suggest that BRG1 is incorporated into transcriptional complexes that are formed by activated Smads in the nucleus, on target promoters. Using BRG1-deficient cell systems(H522 lung cancer cells), we defined the BRG1 dependence of the TGFβ transcriptional program genome-wide. Most TGFβ gene responses in human epithelial cells are dependent on BRG1 function. Remarkably, BRG1 is not required for the TGFβ-mediated induction of SMAD7 and SNON, which encode key mediators of negative feedback in this pathway. Our results provide a genome-wide scope of the participation of BRG1 in TGFβ action and suggest a widespread yet differential involvement of BRG1 SWI/SNF remodeler in the transcriptional response of many genes to this cytokine. Keywords: comparative genomic hybridization

2008-03-18 | GSE10847 | GEO

Smad2 and Smad3 have differential sensitivity in relaying TGF b signaling and inversely regulate early lineage specification

Project description:The transforming growth factor beta (TGFÎ²) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFÎ² signals. Here, we show that Smad3 is an insensitive TGFÎ² transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFÎ² signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFÎ² signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFÎ²/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFÎ² signaling and have distinct roles in regulating early developmental events. GFP, GFP-Smad2 and GFP-Smad3 constitutively expressed Smad3-/- mouse ESCs were differentiated to day6 neuroepithelia and collected for Chip-Seq with an anti-GFP antibody.

2016-03-01 | E-GEOD-76557 | biostudies-arrayexpress

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Comparison of BRG1 reexpression, TSA treatment and 5dAzaC treatment on gene expression in human NCI-H522 NSCLC cells

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Protein-protein interactions of BRG1 or BRG1-HSA in SW13 cells

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2023-02-15 | PXD029647 | Pride

Brd7, a novel PBAF-specific SWI/SNF subunit, is required for gene activation and repression in embryonic stem cells

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2010-03-04 | E-GEOD-7791 | biostudies-arrayexpress

Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodeling complex

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2011-03-07 | E-GEOD-24573 | biostudies-arrayexpress

Smad2 and Smad3 have differential sensitivity in relaying TGF b signaling and inversely regulate early lineage specification

Project description:The transforming growth factor beta (TGFβ) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFβ signals. Here, we show that Smad3 is an insensitive TGFβ transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFβ signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFβ signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFβ/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFβ signaling and have distinct roles in regulating early developmental events.

2016-03-01 | GSE76557 | GEO

Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation [array]

Project description:Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor formation in several cancer types, we found that leukemia cells instead rely on Brg1 to support their oncogenic transcriptional program, which includes Myc as one of its key targets. To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 megabases downstream of Myc that are occupied by SWI/SNF, as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably, these distal Myc enhancers coincide with a region that is focally amplified in 3% of acute myeloid leukemia. Together, these findings define a leukemia maintenance function for SWI/SNF that is linked to enhancer-mediated gene regulation, providing general insights into how cancer cells exploit transcriptional coactivators to maintain oncogenic gene expression programs In order to understanding the transcription regulation network downstream of Brg1 in murine AML, we performed microarray in murine MLL-AF9/NrasG12D cell line under the condition that Brg1 was suppressed by three independent shRNAs for 96h.

2013-12-02 | E-GEOD-52231 | biostudies-arrayexpress

Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation [ChIP-Seq]

Project description:Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor formation in several cancer types, we found that leukemia cells instead rely on Brg1 to support their oncogenic transcriptional program, which includes Myc as one of its key targets. To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 megabases downstream of Myc that are occupied by SWI/SNF, as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably, these distal Myc enhancers coincide with a region that is focally amplified in 3% of acute myeloid leukemia. Together, these findings define a leukemia maintenance function for SWI/SNF that is linked to enhancer-mediated gene regulation, providing general insights into how cancer cells exploit transcriptional coactivators to maintain oncogenic gene expression programs In order to understanding the lineage specific requirement of coactivaor, such as Brg1 and Brd4, in AML, we performed ChIP-seq with Brg1, Brd4 together with histone modification marks in murine MLL-AF9/NrasG12D AML cell line to search tissue specific cis regulation element that can be accounted for the leukemia specific dependence.

2013-12-02 | E-GEOD-52277 | biostudies-arrayexpress

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