The Bromodomain Containing 8 (BRD8) Transcriptional Network in Human Lung Epithelial Cells
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ABSTRACT:
PROVIDER: PRJNA666181 | ENA |
REPOSITORIES: ENA
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Project description:Mechanisms regulating gene expression in the airway epithelium underlie its response to the environment. A network of transcription factors (TFs) and architectural proteins, modulate chromatin accessibility and recruit activating or repressive signals. Bromodomain-containing proteins function as TFs or by engaging methyltransferase or acetyltransferase activity to induce chromatin modifications. Here we investigate the role of Bromodomain Containing 8 (BRD8) in coordinating lung epithelial function. Sites of BRD8 occupancy genome-wide were mapped in human lung epithelial cell lines (Calu-3 and 16HBE14o-). CCCTC-Binding Factor (CTCF) was identified as a predicted co-factor of BRD8, based upon motif over-representation under BRD8 ChIP-seq peaks. Following siRNA-mediated depletion of BRD8, differentially expressed genes with peaks of BRD8 occupancy within 20 kb were subject to gene ontology process enrichment analysis. BRD8 targets are enriched for genes involved in the innate immune response and depletion of BRD8 increased the secretion of the antimicrobial peptide beta-defensin 1 and multiple chemokines.
2021-01-29 | GSE158686 | GEO
Project description:Mechanisms regulating gene expression in the airway epithelium underlie its response to the environment. A network of transcription factors (TFs) and architectural proteins, modulate chromatin accessibility and recruit activating or repressive signals. Bromodomain-containing proteins function as TFs or by engaging methyltransferase or acetyltransferase activity to induce chromatin modifications. Here we investigate the role of Bromodomain Containing 8 (BRD8) in coordinating lung epithelial function. Sites of BRD8 occupancy genome-wide were mapped in human lung epithelial cell lines (Calu-3 and 16HBE14o-). CCCTC-Binding Factor (CTCF) was identified as a predicted co-factor of BRD8, based upon motif over-representation under BRD8 ChIP-seq peaks. Following siRNA-mediated depletion of BRD8, differentially expressed genes with peaks of BRD8 occupancy within 20 kb were subject to gene ontology process enrichment analysis. BRD8 targets are enriched for genes involved in the innate immune response and depletion of BRD8 increased the secretion of the antimicrobial peptide beta-defensin 1 and multiple chemokines.
2021-01-29 | GSE158678 | GEO
Project description:The Bromodomain Containing 8 (BRD8) Transcriptional Network in Human Lung Epithelial Cells [ChIP-seq]
| PRJNA666188 | ENA
Project description:The Bromodomain Containing 8 (BRD8) Transcriptional Network in Human Lung Epithelial Cells [RNA-Seq]
| PRJNA666177 | ENA
Project description:Bromodomain-containing protein 4 (BRD4) is an important epigenetic reader which promotes gene transcription to modulate cell-specific functions and is under intensive investigation for its potential as an anti-tumor therapeutic target. However, the role of BRD4 in non-transformed cells remains unclear. Here we demonstrate that BRD4 is required for the expression of epithelial-specific genes and suppression of stem cell-like properties by binding to the distal regions of epithelial-related genes. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription of epithelial differentiation-specific genes. Interestingly, we show that BRD4 perturbation regulates the expression of Grainy Head-like transcription factor, GRHL3, whose depletion partially mimics BRD4 inhibition and blocks differentiated phenotype. By binding to the distal regions of GRHL3, BRD4 promotes RNA polymerase-II occupancy and thus affects eRNA transcription. Altogether, these findings provide evidence that BRD4 promotes a differentiated epithelial phenotype in non-transformed mammary cells at least in part through the activation of GRHL3 expression.
2016-10-06 | GSE72932 | GEO
Project description:Bromodomain-containing protein 4 (BRD4) is an important epigenetic reader which promotes gene transcription to modulate cell-specific functions and is under intensive investigation for its potential as an anti-tumor therapeutic target. However, the role of BRD4 in non-transformed cells remains unclear. Here we demonstrate that BRD4 is required for the expression of epithelial-specific genes and suppression of stem cell-like properties by binding to the distal regions of epithelial-related genes. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription of epithelial differentiation-specific genes. Interestingly, we show that BRD4 perturbation regulates the expression of Grainy Head-like transcription factor, GRHL3, whose depletion partially mimics BRD4 inhibition and blocks differentiated phenotype. By binding to the distal regions of GRHL3, BRD4 promotes RNA polymerase-II occupancy and thus affects eRNA transcription. Altogether, these findings provide evidence that BRD4 promotes a differentiated epithelial phenotype in non-transformed mammary cells at least in part through the activation of GRHL3 expression.
2016-10-06 | GSE72931 | GEO
Project description:Small molecule inhibitors of the bromodomain and extraterminal (BET) family of proteins are in clinical trials for a variety of cancers, but patient selection strategies are limited. This is due in part to the heterogeneity of response following BET inhibition (BETi), which includes differentiation, senescence, and cell death in subsets of cancer cell lines. To elucidate the dominant features defining response to BETi, we carried out phenotypic and gene expression analysis of both treatment naïve cell lines and engineered tolerant lines. We found that both de novo and acquired tolerance to BET inhibition are driven by the robustness of the apoptotic response and that genetic or pharmacological manipulation of the apoptotic signaling network can modify the phenotypic response to BETi. We further identify that ordered expression of the apoptotic genes BCL2, BCL2L1, and BAD significantly predicts response to BETi. Our findings highlight the role of the apoptotic network in response to BETi, providing a molecular basis for patient stratification and combination therapies. Gene expression profiling of A375 melanoma cells or NOMO-1 AML cells treated with DMSO or the BET inhibitor, CPI203. Also, gene expression profiling of the respective derived BETi-tolerant cells treated with DMSO or CPI203.
2016-01-07 | E-GEOD-69383 | biostudies-arrayexpress
Project description:Proteome analysis of lung epithelial cells of house dust mite-challenged mice. The cells were isolated from frozen tissue section by LASER microdissection.
2019-08-16 | PXD010792 | JPOST Repository
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-01-29 | GSE158688 | GEO
Project description:Small molecule inhibitors of the bromodomain and extraterminal (BET) family of proteins are in clinical trials for a variety of cancers, but patient selection strategies are limited. This is due in part to the heterogeneity of response following BET inhibition (BETi), which includes differentiation, senescence, and cell death in subsets of cancer cell lines. To elucidate the dominant features defining response to BETi, we carried out phenotypic and gene expression analysis of both treatment naïve cell lines and engineered tolerant lines. We found that both de novo and acquired tolerance to BET inhibition are driven by the robustness of the apoptotic response and that genetic or pharmacological manipulation of the apoptotic signaling network can modify the phenotypic response to BETi. We further identify that ordered expression of the apoptotic genes BCL2, BCL2L1, and BAD significantly predicts response to BETi. Our findings highlight the role of the apoptotic network in response to BETi, providing a molecular basis for patient stratification and combination therapies.
2016-01-07 | GSE69383 | GEO