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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 [ChIP-seq]

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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

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

| PRJNA1103827 | ENA

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]

| PRJNA1103829 | ENA

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]

| PRJNA1103834 | ENA

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

Project description:Sequencing-based mapping of ensemble pairwise interactions among regulatory elements support the existence of topological assemblies known as promoter-enhancer hubs or cliques in cancer. Yet, prevalence, regulators, and functions of promoter-enhancer hubs in individual cancer cells 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 promoters and enhancers within spatial hubs. Our single-allele studies further demonstrated that lineage-determining SOX9 and signaling-dependent NOTCH1 transcription factors compact MYC and SOX9 hubs. Together, our findings suggest that promoter-enhancer hubs are dynamic and heterogeneous topological assemblies, which are controlled by oncogenic transcription factors and facilitate subtype-restricted gene expression in cancer.

| S-EPMC11305386 | biostudies-literature

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

Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance (HiC)

Project description:Recent advances in high-resolution mapping of spatial interactions among regulatory elements support the existence of complex topological assemblies of enhancers and promoters known as enhancer-promoter hubs or cliques. Yet, organization principles of these multi-interacting enhancer-promoter hubs and their potential role in regulating gene expression in cancer remains unclear. Here, we systematically identified enhancer-promoter hubs in breast cancer, lymphoma, and leukemia. We found that highly interacting enhancer-promoter hubs form at key oncogenes and lineage-associated transcription factors potentially promoting oncogenesis of these diverse cancer types. Genomic and optical mapping of interactions among enhancer and promoter elements further showed that topological alterations in hubs coincide with transcriptional changes underlying acquired resistance to targeted therapy in T cell leukemia and B cell lymphoma. Together, our findings suggest that enhancer-promoter hubs are dynamic and heterogeneous topological assemblies with the potential to control gene expression circuits promoting oncogenesis and drug resistance.

2024-08-16 | GSE268226 | GEO

Enhancer Cis Elements Instruct Promoter-Enhancer Interaction, Promoter-Enhancer Insulation and Compartmental Segregation

Project description:Enhancers harbor instructions encoded for the interactions between cis-elements and transcription factors to orchestrate lineage specific gene programs. Here we developed a modified method for chromosome conformation capture (3C), named MID Hi-C, to reveal how in mouse embryonic stem cells differential cooperation of enhancers and the chromatin remodeler BAF, as instructed by the underlying transcription factor motifs, modulate enhancer-promoter communication. We show that BAF-dependent enhancers permit genomic interactions beyond enhancer boundaries. BAF-dependent enhancers do not dictate genomic interactions within enhancer-promoter loop domains but rather act to instruct remote enhancer-promoter communication. In contrast, BAF-independent enhancers interact with promoter regions within tightly insulated enhancer-promoter loop domains that are marked by promoter and enhancer boundary elements. In addition, enhancer activeness modulated by BAF enforces compartment segregation. Based on these observations, we propose that enhancer cis elements instruct with great precision BAF-induced enhancer-promoter communication and compartmental segregation.

2023-12-31 | GSE213501 | GEO

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