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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268228 | GEO | 2024/08/16

REPOSITORIES: GEO

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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-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance (RNA-Seq)

2024-08-16 | GSE268227 | GEO

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

2024-08-16 | GSE268225 | GEO

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

2024-08-16 | GSE268224 | GEO

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

Project description:Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance

| PRJNA1115203 | ENA

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

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

| PRJNA1115206 | ENA

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

Project description:Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance (RNA-Seq)

| PRJNA1115208 | ENA

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

Project description:Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance (ChIP-Seq)

| PRJNA1115207 | ENA

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

Project description:Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance (ATAC-Seq)

| PRJNA1115205 | ENA

Multi-enhancer transcriptional hubs confer phenotypic robustness.

Project description:We previously showed in Drosophila melanogaster embryos that low-affinity Ultrabithorax (Ubx)-responsive shavenbaby (svb) enhancers drive expression using localized transcriptional environments and that active svb enhancers on different chromosomes tended to colocalize (Tsai et al., 2017). Here, we test the hypothesis that these multi-enhancer 'hubs' improve phenotypic resilience to stress by buffering against decreases in transcription factor concentrations and transcriptional output. Deleting a redundant enhancer from the svb locus led to reduced trichome numbers in embryos raised at elevated temperatures. Using high-resolution fluorescence microscopy, we observed lower Ubx concentration and transcriptional output in this deletion allele. Transcription sites of the full svb cis-regulatory region inserted into a different chromosome colocalized with the svb locus, increasing Ubx concentration, the transcriptional output of svb, and partially rescuing the phenotype. Thus, multiple enhancers could reinforce a local transcriptional hub to buffer against environmental stresses and genetic perturbations, providing a mechanism for phenotypical robustness.

| S-EPMC6650246 | biostudies-literature

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