Transcriptional profiling of Lung H1299-BRG1 inducible cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE35168 | GEO | 2012/03/12
SECONDARY ACCESSION(S): PRJNA150803
REPOSITORIES: GEO
Similar Datasets
Project description:Global Transcriptional analysis of BRG1 in lung cancer cells Comparative transcriptional profile comparing the expression in lung cancer cells before and after restoring the wild type BRG1 or mutant BRG1 expression controlled by the Tet-ON system (doxycycline depending expression)
2012-03-12 | E-GEOD-35168 | biostudies-arrayexpress
Project description:Global Transcriptional analysis of BRG1 in lung cancer cells Comparative transcriptional profile comparing the expression in lung cancer cells before and after restoring the wild type BRG1 or mutant BRG1 expression controlled by the Tet-ON system (doxycycline depending expression)
| S-ECPF-GEOD-35168 | biostudies-other
Project description:Gupta M, Concepcion CP, Fahey CG, Keshishian H, Bhutkar A, Brainson CF, Sanchez-Rivera FJ, Pessina P, Kim JY, Simoneau A, Paschini M, Beytagh MC, Stanclift C, Schenone M, Mani DR, Li C, Oh A, Li F, Hu H, Karatza A, Bronson RT, Shaw AT, Hata AN, Wong K, Zou L, Carr SA, Jacks T, Kim CF. Cancer Res 2020.
Inactivation of SMARCA4/BRG1, the core ATPase subunit of mammalian SWI/SNF
complexes, occurs at very high frequencies in non-small cell lung cancers. There are no
targeted therapies for this subset of lung cancers, nor is it known how mutations in BRG1
contribute to lung cancer progression. Using a combination of gain- and loss-of-function
approaches, we demonstrate that deletion of BRG1 in lung cancer leads to activation of
replication stress responses. Single-molecule assessment of replication fork dynamics in
BRG1-deficient cells revealed increased origin firing, mediated through pre-licensing protein
CDC6. Quantitative mass spectrometry and co-immunoprecipitation assays showed that
BRG1-containing SWI/SNF complexes interact with RPA complexes. Lastly, we show that
BRG1-deficient lung cancers are sensitive to the pharmacological inhibition of ATR. These
findings provide novel mechanistic insight into BRG1-mutant lung cancers and suggest that
their ATR dependency can be leveraged therapeutically, and potentially expanded to BRG1-
mutant cancers in other tissues.
2020-07-08 | MSV000085701 | MassIVE
Project description:Background/Objectives: BRG1 loss-of-function (LOF) mutation is found in ~10% non-small cell lung cancer (NSCLC) but its role in lung tumorigenesis is unclear and investigated in this study. Methods: BRG1-knockout (KO) lines were generated from various non-malignant, pre-malignant, and malignant human lung epithelia-derived cell lines using CRISPR. Effects of BRG1-KO on cell growth, transcriptome, methylome, and epigenetic therapy were compared with wild-type (BRG1-WT) isogenic controls using standard in vitro and in vivo assays. Results: BRG1 protein was expressed in all non/pre-malignant lung epithelial cells but lost in 47% (14/30) of NSCLC cell lines. BRG1-KO and cigarette smoke (CS) exposure individually transformed human bronchial epithelial cell lines (HBECs) as evident by anchorage-independent growth. BRG1-KO and CS produced additive to synergistic effects on sensitivity to transformation that differed across HBECs. RNA-seq analysis revealed BRG1-KO significantly changed expression of over 8,500 genes on average impacting lung development, function, damage repair and cancer pathways including axonal guidance, pulmonary wound healing, and epithelial-to-mesenchymal transition (EMT). BRG1-KO also led to hypermethylation of >47,000 promoter CpGs within ~9,500 genes on average in different HBECs that included silencing of epithelial genes involved in EMT and tumor suppressor genes. BRG1-KO also moderately increased the in vitro and in vivo sensitivity of NSCLC cells to some epigenetic drugs. Conclusion: BRG1-LOF is frequent in NSCLC, can drive transformation of lung epithelial cells to acquire properties of premalignant cells indicating a potential role in lung cancer initiation, and sensitizes lung tumors to epigenetic therapy.
2025-11-14 | GSE307857 | GEO
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
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
Project description:Mammalian SWI/SNF-related complexes have been implicated in cancer based on some of the subunits physically interacting with RB and other proteins involved in carcinogenesis. Additionally, several subunits are mutated or not expressed in tumor-derived cell lines. Strong evidence for a role in tumorigenesis in vivo, however, has been limited to SNF5 mutations that result primarily in malignant rhabdoid tumors (MRTs) in humans and MRTs as well as other sarcomas in mice. We previously generated a null mutation of the Brg1 catalytic subunit in the mouse and reported that homozygotes die during embryogenesis. Here, we demonstrate that Brg1 heterozygotes are susceptible to mammary tumors that are fundamentally different than Snf5 tumors. First, mammary tumors are carcinomas not sarcomas. Second, Brg1+/- tumors arise because of haploinsufficiency rather than loss of heterozygosity (LOH). Third, Brg1+/- tumors exhibit genomic instability but not polyploidy based on array CGH results. We monitored Brg1+/-, Brm-/- double-mutant mice but did not observe any tumors resembling those from Snf5 mutants, indicating that the Brg1+/- and Snf5+/- tumor phenotypes do not differ simply because Brg1 has a closely related paralog whereas Snf5 does not. These findings demonstrate that BRG1 and SNF5 are not functionally equivalent but protect against cancer in different ways. We also demonstrate that Brg1+/- mammary tumors have relatively heterogeneous gene expression profiles with similarities and differences compared to other mouse models of breast cancer. The Brg1+/- expression profiles are not particularly similar to mammary tumors from Wap-T121 transgenic line where RB is perturbed. We were also unable to detect a genetic interaction between the Brg1+/- and Rb+/- tumor phenotypes. These latter findings do not support a BRG1-RB interaction in vivo. Experiment Overall Design: 14 microarrays consisting of 12 unique Brg1+/- murine mammary Experiment Overall Design: tumors
2008-06-18 | E-GEOD-8516 | biostudies-arrayexpress
Project description:The chromatin status fluctuates with effector and memory group 2 innate lymphoid cell (ILC2) responses. How this intricate coordination affects allergic lung inflammation remains unclear. Here, we report that during papain-induced lung inflammation, the expression of chromatin remodeler Brg1 is upregulated by IL-33 in ILC2s, accompanied with more open chromatin regions having increased accessibility. Brg1 expression is also upregulated in asthma patients’ ILC2s. Ablating Brg1 constrains ILC2 expansion and ameliorates both acute and alarmin-rechallenged secondary lung inflammation. Mechanistically, Brg1 imprints the chromatin landscape favoring aerobic glycolysis, the metabolic process reinforced in effector and memory ILC2s, to facilitate ILC2 expansion. Particularly, Brg1-augmented Hif1a enhancer accessibility is a sustained epigenetic signature in memory ILC2s inherited from effector ILC2s, and Hif1a enhances effector and memory ILC2 responses. Pharmacological inhibition of Brg1, rather than dexamethasone treatment, in acute phase is sufficient to alleviate secondary lung inflammation, highlighting Brg1 as a promising therapeutic target.
2025-09-17 | GSE279674 | GEO
Project description:To development our gene expression approach , we have employed whole genome microarray expression profiling as a discovery platform to identify genes potentialy regulated by the treatment with glucocorticoids (GC) and retinoic acid (RA) alone and combined with AZA/SAHA and the relationship of these features with the status of BRG1 and MYC in lung cancer cell lines. MYC amplified cell lines and BRG1 mutant cell lines were treated with glucocorticoids (GC) and retinoic acid (RA) alone and combined with AZA/SAHA and their expression was then measured
2016-09-08 | E-GEOD-66244 | biostudies-arrayexpress
Project description:BRG1 loss is frequent in lung cancer and transforms lung epi-thelial cells via transcriptional and epigenetic reprograming
| PRJNA1327420 | ENA