Similar Datasets
Project description:Dysregulation of enhancer-promoter communication in the context of the three-dimensional (3D) nucleus is increasingly recognized as a potential driver of oncogenic programs. Here, we profiled the 3D enhancer-promoter networks of primary patient-derived glioblastoma stem cells (GSCs) in comparison with neuronal stem cells (NSCs) to identify potential central nodes and vulnerabilities in the regulatory logic of this devastating cancer. Specifically, we focused on hyperconnected 3D regulatory hubs and demonstrated that hub-interacting genes exhibit high and coordinated expression at the single-cell level and strong association with oncogenic programs that distinguish IDH-wt glioblastoma patients from low-grade glioma. Epigenetic silencing of a recurrent 3D enhancer hub-with an uncharacterized role in glioblastoma-was sufficient to cause concordant downregulation of multiple hub-connected genes along with significant shifts in transcriptional states and reduced clonogenicity. By integrating published datasets from other cancer types, we also identified both universal and cancer type-specific 3D regulatory hubs which enrich for varying oncogenic programs and nominate specific factors associated with worse outcomes. Genetic alterations, such as focal duplications, could explain only a small fraction of the detected hyperconnected hubs and their increased activity. Overall, our study provides computational and experimental support for the potential central role of 3D regulatory hubs in controlling oncogenic programs and properties.
| S-EPMC11875237 | biostudies-literature
Project description:Enhancer-promoter communication in the context of the three-dimensional (3D) nucleus is critical for the regulation of transcriptional programs specific for cell identity. Here, we profile the 3D enhancer-promoter networks of primary patient-derived human glioma spheres (GSCs) in comparison with neuronal stem cells to identify candidate central nodes of GSC tumorigenic programs. We have identified highly interacting 3D enhancer-promoter “hubs” which strongly associate with robust and coordinated expression of tumor-associated genes, suggesting potentially central roles in the regulation of oncogenic programs. Integration of whole-genome sequencing (WGS) data from The Cancer Genome Atlas showed that 3D regulatory hubs are strongly enriched for recurrent point mutations in the larger cohort of glioblastoma patients. In a proof-of-concept experiment, epigenetic perturbation of a highly interacting and recurrent 3D enhancer hub in the GOLIM4 locus led to significant downregulation of multiple hub-connected genes and reduced clonogenicity along with a global shift in the transcriptional states. Finally, integration of published H3K27ac HiChIP from other cancer types enabled the identification of both “universal” and cancer type-specific 3D regulatory hubs which enrich for different oncogenic programs and potential regulators, and often associate with a worse prognosis. Overall, our study identifies complex 3D regulatory hubs in glioblastoma and provides computational and experimental support for their potential role in driving oncogenic programs and promoting tumorigenic properties.
2025-03-06 | GSE260526 | GEO
Project description:Enhancer-promoter communication in the context of the three-dimensional (3D) nucleus is critical for the regulation of transcriptional programs specific for cell identity. Here, we profile the 3D enhancer-promoter networks of primary patient-derived human glioma spheres (GSCs) in comparison with neuronal stem cells to identify candidate central nodes of GSC tumorigenic programs. We have identified highly interacting 3D enhancer-promoter “hubs” which strongly associate with robust and coordinated expression of tumor-associated genes, suggesting potentially central roles in the regulation of oncogenic programs. Integration of whole-genome sequencing (WGS) data from The Cancer Genome Atlas showed that 3D regulatory hubs are strongly enriched for recurrent point mutations in the larger cohort of glioblastoma patients. In a proof-of-concept experiment, epigenetic perturbation of a highly interacting and recurrent 3D enhancer hub in the GOLIM4 locus led to significant downregulation of multiple hub-connected genes and reduced clonogenicity along with a global shift in the transcriptional states. Finally, integration of published H3K27ac HiChIP from other cancer types enabled the identification of both “universal” and cancer type-specific 3D regulatory hubs which enrich for different oncogenic programs and potential regulators, and often associate with a worse prognosis. Overall, our study identifies complex 3D regulatory hubs in glioblastoma and provides computational and experimental support for their potential role in driving oncogenic programs and promoting tumorigenic properties.
2025-03-06 | GSE260529 | GEO
Project description:Enhancer-promoter communication in the context of the three-dimensional (3D) nucleus is critical for the regulation of transcriptional programs specific for cell identity. Here, we profile the 3D enhancer-promoter networks of primary patient-derived human glioma spheres (GSCs) in comparison with neuronal stem cells to identify candidate central nodes of GSC tumorigenic programs. We have identified highly interacting 3D enhancer-promoter “hubs” which strongly associate with robust and coordinated expression of tumor-associated genes, suggesting potentially central roles in the regulation of oncogenic programs. Integration of whole-genome sequencing (WGS) data from The Cancer Genome Atlas showed that 3D regulatory hubs are strongly enriched for recurrent point mutations in the larger cohort of glioblastoma patients. In a proof-of-concept experiment, epigenetic perturbation of a highly interacting and recurrent 3D enhancer hub in the GOLIM4 locus led to significant downregulation of multiple hub-connected genes and reduced clonogenicity along with a global shift in the transcriptional states. Finally, integration of published H3K27ac HiChIP from other cancer types enabled the identification of both “universal” and cancer type-specific 3D regulatory hubs which enrich for different oncogenic programs and potential regulators, and often associate with a worse prognosis. Overall, our study identifies complex 3D regulatory hubs in glioblastoma and provides computational and experimental support for their potential role in driving oncogenic programs and promoting tumorigenic properties.
2025-03-24 | GSE280831 | GEO
Project description:Enhancer-promoter communication in the context of the three-dimensional (3D) nucleus is critical for the regulation of transcriptional programs specific for cell identity. Here, we profile the 3D enhancer-promoter networks of primary patient-derived human glioma spheres (GSCs) in comparison with neuronal stem cells to identify candidate central nodes of GSC tumorigenic programs. We have identified highly interacting 3D enhancer-promoter “hubs” which strongly associate with robust and coordinated expression of tumor-associated genes, suggesting potentially central roles in the regulation of oncogenic programs. Integration of whole-genome sequencing (WGS) data from The Cancer Genome Atlas showed that 3D regulatory hubs are strongly enriched for recurrent point mutations in the larger cohort of glioblastoma patients. In a proof-of-concept experiment, epigenetic perturbation of a highly interacting and recurrent 3D enhancer hub in the GOLIM4 locus led to significant downregulation of multiple hub-connected genes and reduced clonogenicity along with a global shift in the transcriptional states. Finally, integration of published H3K27ac HiChIP from other cancer types enabled the identification of both “universal” and cancer type-specific 3D regulatory hubs which enrich for different oncogenic programs and potential regulators, and often associate with a worse prognosis. Overall, our study identifies complex 3D regulatory hubs in glioblastoma and provides computational and experimental support for their potential role in driving oncogenic programs and promoting tumorigenic properties.
2025-03-06 | GSE260907 | GEO
Project description:Enhancer-promoter communication in the context of the three-dimensional (3D) nucleus is critical for the regulation of transcriptional programs specific for cell identity. Here, we profile the 3D enhancer-promoter networks of primary patient-derived human glioma spheres (GSCs) in comparison with neuronal stem cells to identify candidate central nodes of GSC tumorigenic programs. We have identified highly interacting 3D enhancer-promoter “hubs” which strongly associate with robust and coordinated expression of tumor-associated genes, suggesting potentially central roles in the regulation of oncogenic programs. Integration of whole-genome sequencing (WGS) data from The Cancer Genome Atlas showed that 3D regulatory hubs are strongly enriched for recurrent point mutations in the larger cohort of glioblastoma patients. In a proof-of-concept experiment, epigenetic perturbation of a highly interacting and recurrent 3D enhancer hub in the GOLIM4 locus led to significant downregulation of multiple hub-connected genes and reduced clonogenicity along with a global shift in the transcriptional states. Finally, integration of published H3K27ac HiChIP from other cancer types enabled the identification of both “universal” and cancer type-specific 3D regulatory hubs which enrich for different oncogenic programs and potential regulators, and often associate with a worse prognosis. Overall, our study identifies complex 3D regulatory hubs in glioblastoma and provides computational and experimental support for their potential role in driving oncogenic programs and promoting tumorigenic properties.
2025-03-06 | GSE260528 | GEO
Project description:Enhancer-promoter communication in the context of the three-dimensional (3D) nucleus is critical for the regulation of transcriptional programs specific for cell identity. Here, we profile the 3D enhancer-promoter networks of primary patient-derived human glioma spheres (GSCs) in comparison with neuronal stem cells to identify candidate central nodes of GSC tumorigenic programs. We have identified highly interacting 3D enhancer-promoter “hubs” which strongly associate with robust and coordinated expression of tumor-associated genes, suggesting potentially central roles in the regulation of oncogenic programs. Integration of whole-genome sequencing (WGS) data from The Cancer Genome Atlas showed that 3D regulatory hubs are strongly enriched for recurrent point mutations in the larger cohort of glioblastoma patients. In a proof-of-concept experiment, epigenetic perturbation of a highly interacting and recurrent 3D enhancer hub in the GOLIM4 locus led to significant downregulation of multiple hub-connected genes and reduced clonogenicity along with a global shift in the transcriptional states. Finally, integration of published H3K27ac HiChIP from other cancer types enabled the identification of both “universal” and cancer type-specific 3D regulatory hubs which enrich for different oncogenic programs and potential regulators, and often associate with a worse prognosis. Overall, our study identifies complex 3D regulatory hubs in glioblastoma and provides computational and experimental support for their potential role in driving oncogenic programs and promoting tumorigenic properties.
2025-03-06 | GSE260527 | GEO
Project description:Three-dimensional regulatory hubs support oncogenic programs in glioblastoma
| PRJNA1081944 | ENA
Project description:Three-dimensional regulatory hubs support oncogenic programs in glioblastoma
| PRJNA1090165 | ENA
Project description:Three-dimensional regulatory hubs support oncogenic programs in glioblastoma [HiChIP]
| PRJNA1081946 | ENA