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Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells [CUT&RUN]

ABSTRACT: Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells [CUT&RUN]

PROVIDER: PRJNA1103835 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28786368_1.fastq.gz	Fastqsanger.gz
	SRR28786368_2.fastq.gz	Fastqsanger.gz
	SRR28786369_1.fastq.gz	Fastqsanger.gz
	SRR28786369_2.fastq.gz	Fastqsanger.gz
	SRR28786370_1.fastq.gz	Fastqsanger.gz

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Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells [CUT&RUN]

Project description:Recent sequencing-based experiments mapping ensemble interaction frequency among regulatory elements in cancer cells support the existence of complex topological assemblies of enhancers and promoters known as promoter-enhancer hubs or cliques. Yet, the prevalence of promoter-enhancer hubs in individual cells, factors regulating their dynamics and assembly, as well as their role in transcriptional dysregulation in cancer remain unclear. Here, we systematically integrated functional genomics, transcription factor screening, and optical mapping of promoter-enhancer interactions to identify key promoter-enhancer hubs, examine heterogeneity of their assembly, determine their regulators, and elucidate their role in gene expression control in individual triple negative breast cancer (TNBC) cells. Optical mapping of individual SOX9 and MYC alleles revealed the existence of frequent multiway interactions among gene promoters and enhancers within promoter-enhancer hubs. Our single-allele studies further demonstrated that lineage-determining SOX9 and signaling-dependent NOTCH1 transcription factors compact MYC and SOX9 promoter-enhancer hubs, respectively. Together, our findings suggest that promoter-enhancer hubs are dynamic and heterogeneous topological assemblies controlled by oncogenic transcription factors potentially in a cancer subtype-restricted manner to facilitate aberrant gene expression.

2024-08-16 | GSE264706 | GEO

Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells [RNA-seq]

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Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells [ChIP-seq]

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Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells

Project description:Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells

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Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells [RNA-seq]

Project description:Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells [RNA-seq]

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Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells [ChIP-seq]

Project description:Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells [ChIP-seq]

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Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-08-16 | GSE264708 | GEO

Three-dimensional regulatory hubs support oncogenic programs in glioblastoma [HiChIP]

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.

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Three-dimensional regulatory hubs support oncogenic programs in glioblastoma [RNA-seq]

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Three-dimensional regulatory hubs support oncogenic programs in glioblastoma [scRNA-seq]

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