Dynamic and integrated transcriptional code orchestrates the angiogenic response [Nanostring]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA431548 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Dynamic and integrated transcriptional code orchestrates the angiogenic response
| PRJNA431549 | ENA
Project description:Epigenetic modifications and transcription factors form a chromatin code to regulate gene expression in many physiological and pathological processes. However, little is known about whether the environmental stimuli could interplay with this code and regulate the transcription and biological functions. Here, we interrogated the chromatin state of multiple epigenetic modifications and transcription factors during a time course of VEGF stimulation in the endothelial cells and found a broad change of transcriptome induced by VEGF. At the promoter-proximal regions, a unique epigenetic pattern of bivalent domain preferentially governed the part of transcriptome change by hijacking the EZH1 transcriptional activity. VEGF substantially altered the epigenetic landscape at enhancer regions and transcription factor chromatin occupancy across the genome, which significantly accounted for the change of VEGF-downstream gene expression. Moreover, by integrating a transcription-regulatory network of VEGF pathway, we discovered MAFs as a novel mater transcriptional factor controlling the VEGF transcriptional program and angiogenesis. Collectively, these results revealed the extracellular stimulus of VEGF in fact implements a significant reconfiguration of chromatin code that coordinately regulates the angiogenic response.
2018-03-28 | GSE109623 | GEO
Project description:Dynamic and integrated transcriptional code orchestrates the angiogenic response [Seq]
| PRJNA431557 | ENA
Project description:Epigenetic modifications and transcription factors form a chromatin code to regulate gene expression in many physiological and pathological processes. However, little is known about whether the environmental stimuli could interplay with this code and regulate the transcription and biological functions. Here, we interrogated the chromatin state of multiple epigenetic modifications and transcription factors during a time course of VEGF stimulation in the endothelial cells and found a broad change of transcriptome induced by VEGF. At the promoter-proximal regions, a unique epigenetic pattern of bivalent domain preferentially governed the part of transcriptome change by hijacking the EZH1 transcriptional activity. VEGF substantially altered the epigenetic landscape at enhancer regions and transcription factor chromatin occupancy across the genome, which significantly accounted for the change of VEGF-downstream gene expression. Moreover, by integrating a transcription-regulatory network of VEGF pathway, we discovered MAFs as a novel mater transcriptional factor controlling the VEGF transcriptional program and angiogenesis. Collectively, these results revealed the extracellular stimulus of VEGF in fact implements a significant reconfiguration of chromatin code that coordinately regulates the angiogenic response.
2018-03-28 | GSE109625 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-03-28 | GSE109626 | GEO
Project description:Alveolar soft part sarcoma (ASPS) is a rare soft part malignancy affecting adolescents and young adult. ASPS is characterized by its alveolar structure consisting of tumor cells and highly integrated vascular network, and its high metastatic potential indicates the importance of the prominent angiogenic activity of ASPS. Here we find that the expression of ASPSCR1-TFE3, the fusion transcription factor causatively associated with ASPS, is dispensable for in vitro tumor maintenance but required for in vivo tumor development via angiogenesis. ASPSCR1-TFE3 frequently associates with active enhancers including super-enhancers (SE) upon its DNA binding, and the loss of its expression induces dynamic modification of SE distribution related to genes belonging to the angiogenesis pathway. Using epigenomic CRISPR/dCas9 screening, we identify Pdgfb, Rab27a, Sytl2, and Vwf as critical target genes associated with reduced enhancer activities due to the ASPSCR1-TFE3 loss. ASPSCR1-TFE3 thus orchestrates higher ordered angiogenesis via enhanced intracellular trafficking of angiogenic factors.
2023-01-20 | GSE215316 | GEO
Project description:Alveolar soft part sarcoma (ASPS) is a rare soft part malignancy affecting adolescents and young adult. ASPS is characterized by its alveolar structure consisting of tumor cells and highly integrated vascular network, and its high metastatic potential indicates the importance of the prominent angiogenic activity of ASPS. Here we find that the expression of ASPSCR1-TFE3, the fusion transcription factor causatively associated with ASPS, is dispensable for in vitro tumor maintenance but required for in vivo tumor development via angiogenesis. ASPSCR1-TFE3 frequently associates with active enhancers including super-enhancers (SE) upon its DNA binding, and the loss of its expression induces dynamic modification of SE distribution related to genes belonging to the angiogenesis pathway. Using epigenomic CRISPR/dCas9 screening, we identify Pdgfb, Rab27a, Sytl2, and Vwf as critical target genes associated with reduced enhancer activities due to the ASPSCR1-TFE3 loss. ASPSCR1-TFE3 thus orchestrates higher ordered angiogenesis via enhanced intracellular trafficking of angiogenic factors.
2023-01-16 | GSE189163 | GEO
Project description:Alveolar soft part sarcoma (ASPS) is a rare soft part malignancy affecting adolescents and young adult. ASPS is characterized by its alveolar structure consisting of tumor cells and highly integrated vascular network, and its high metastatic potential indicates the importance of the prominent angiogenic activity of ASPS. Here we find that the expression of ASPSCR1-TFE3, the fusion transcription factor causatively associated with ASPS, is dispensable for in vitro tumor maintenance but required for in vivo tumor development via angiogenesis. ASPSCR1-TFE3 frequently associates with active enhancers including super-enhancers (SE) upon its DNA binding, and the loss of its expression induces dynamic modification of SE distribution related to genes belonging to the angiogenesis pathway. Using epigenomic CRISPR/dCas9 screening, we identify Pdgfb, Rab27a, Sytl2, and Vwf as critical target genes associated with reduced enhancer activities due to the ASPSCR1-TFE3 loss. ASPSCR1-TFE3 thus orchestrates higher ordered angiogenesis via enhanced intracellular trafficking of angiogenic factors. We used microarrays to detail the global program of gene expression in mouse and human ASPS cells.
2023-01-20 | GSE186789 | GEO
Project description:Alveolar soft part sarcoma (ASPS) is a rare soft part malignancy affecting adolescents and young adult. ASPS is characterized by its alveolar structure consisting of tumor cells and highly integrated vascular network, and its high metastatic potential indicates the importance of the prominent angiogenic activity of ASPS. Here we find that the expression of ASPSCR1-TFE3, the fusion transcription factor causatively associated with ASPS, is dispensable for in vitro tumor maintenance but required for in vivo tumor development via angiogenesis. ASPSCR1-TFE3 frequently associates with active enhancers including super-enhancers (SE) upon its DNA binding, and the loss of its expression induces dynamic modification of SE distribution related to genes belonging to the angiogenesis pathway. Using epigenomic CRISPR/dCas9 screening, we identify Pdgfb, Rab27a, Sytl2, and Vwf as critical target genes associated with reduced enhancer activities due to the ASPSCR1-TFE3 loss. ASPSCR1-TFE3 thus orchestrates higher ordered angiogenesis via enhanced intracellular trafficking of angiogenic factors. We used microarrays to detail the global program of gene expression in mouse and human ASPS cells.
2023-01-20 | GSE215264 | GEO
Project description:Signal-responsive gene expression is essential for vascular growth and patterning, yet the mechanisms allowing the integration of signaling inputs and transcriptional activities are largely unknown. Here we show that RNF20, the major E3 ubiquitin ligase of histone H2B, plays a key role during sprouting angiogenesis by mediating Pol II promoter-proximal pausing at pro-angiogenic genes. Furthermore, it orchestrates large-scale mRNA processing events, which change the bioavailability and function of critical pro-angiogenic factors, such as VEGFA. Mechanistically, we show that RNF20 restricts ERG-dependent gene activation through the VEGF-ERK1/2 axis while enabling Notch1 to bind to chromatin, thereby modulating the VEGF-Notch signaling circuits. Since perturbations of RNF20 are associated with cardiovascular malformations in human patients, our work may provide novel therapeutic avenues for diseases caused by vascular dysfunction.
2024-08-18 | GSE246811 | GEO