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

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE10847 | GEO | 2008/03/18

SECONDARY ACCESSION(S): PRJNA107337

REPOSITORIES: GEO

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Transcription profiling of human NCI-H522

Project description: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.

2008-04-05 | E-GEOD-10847 | biostudies-arrayexpress

Genome-wide profile of the SWI/SNF chromatin remodeling complex

Project description:A systems understanding of nuclear organization and events is critical for determining how cells divide, differentiate and respond to stimuli and for identifying the causes of diseases. Chromatin remodeling complexes such as SWI/SNF have been implicated in a wide variety of cellular processes including gene expression, nuclear organization, centromere function and chromosomal stability, and mutations in SWI/SNF components have been linked to several types of cancer. To better understand the biological processes in which chromatin remodeling proteins participate we globally mapped binding regions for several components of the SWI/SNF complex throughout the human genome using ChIP-Seq. SWI/SNF components were found to lie near regulatory elements integral to transcription (e.g. 5M-bM-^@M-^Y ends, RNA Polymerases II and III and enhancers) as well as regions critical for chromosome organization (e.g. CTCF, lamins and DNA replication origins). To further elucidate the association of SWI/SNF subunits with each other as well as with other nuclear proteins we also analyzed SWI/SNF immunoprecipitated complexes by mass spectrometry. Individual SWI/SNF factors are associated with their own family members as well as with cellular constituents such as nuclear matrix proteins, key transcription factors and centromere components implying a ubiquitous role in gene regulation and nuclear function. We find an overrepresentation of both SWI/SNF-associated regions and proteins in cell cycle and chromosome organization. Taken together the results from our ChIP and immunoprecipitation experiments suggest that SWI/SNF facilitates gene regulation and genome function more broadly and through a greater diversity of interactions than previously appreciated. ChIP-Seq analysis of the SWI/SNF subunits Ini1, Brg1, BAF155 and BAF170 in HeLa S3 cells

2011-01-10 | E-GEOD-24397 | biostudies-arrayexpress

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

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2016-03-01 | GSE76557 | GEO

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

BAF Complex Enhances Reprogramming of Adult Human Fibroblasts

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2018-11-29 | GSE75568 | GEO

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Project description:The SWI/SNF complex remodels chromatin in an ATP-dependent manner through the ATPase subunits BRG1 and BRM. Chromatin remodeling alters nucleosome structure to change gene expression, however aberrant remodeling and gene expression can result in cancer. The function and localization on chromatin of the SWI/SNF complex depends on the protein makeup of the complex. Here we report the protein-protein interactions of wild-type BRG1 or mutant BRG1 in which the HSA domain has been deleted (BRG1-HSA). We demonstrate the interaction of BRG1 with most SWI/SNF complex members and a failure of a number of these members to interact with BRG1-HSA. These results demonstrate that the HSA domain of BRG1 is a critical interaction platform for the correct formation of SWI/SNF remodeling complexes.

2023-02-15 | PXD029647 | Pride

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

Chromatin regulation by BAF170 controls cerebral cortical size and thickness.

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2013-05-02 | E-GEOD-45629 | biostudies-arrayexpress

Comparison of gene expression in skeletal muscle between Baf155 WT and mutant

Project description:Baf155 is a core subunit of SWI/SNF complex, an ATP dependent chromatin remodeler. To explore the function of Baf155 in skeletal muscle, we deleted the Baf155 in skeletal muscle and compared the gene expression profiling between wild type control and Baf155 deleted mutant mice.

2023-07-25 | GSE163373 | GEO

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

Project description:Tissue-specific transcription factors initiate differentiation toward a specialized cell type by inducing transcription-permissive chromatin modifications at target gene promoters, through the recruitment of the SWI/SNF chromatin-remodeling complex (1, 2). The molecular mechanism that regulates the chromatin re-distribution of SWI/SNF in response to differentiation signals is currently unknown. Here we show that the muscle determination factor MyoD and the SWI/SNF structural sub-unit, BAF60c (SMARCD3), form a complex on the regulatory elements of MyoD-target genes in undifferentiated myoblasts, prior to the activation of gene expression. MyoD-BAF60c complex is devoid of the ATP-dependent enzymatic sub-units Brg1 and Brm, is required for stable MyoD binding to Ebox sequences, and marks the chromatin for signal-dependent recruitment of the SWI/SNF core complex to muscle loci. BAF60c phosphorylation on a conserved threonine by differentiation-activated p38 signalling promotes the incorporation of MyoD-BAF60c into a Brg1-based SWI/SNF complex, which is competent to remodel the chromatin and activates transcription of MyoD-target genes. Our data support an unprecedented two-step model, by which pre-assembled BAF60c-MyoD complex directs the SWI/SNF complex chromatin re-distribution to muscle loci in response to differentiation cues. Differentiation of C2C12 cells individually interfered for BRG1, BAF60B, BAF60C

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

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