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

Brent S. Perlman, Noah Burget, Yeqiao Zhou, Gregory W. Schwartz, Jelena Petrovic, Zora Modrusan and Robert B. Faryabi ()
Additional contact information
Brent S. Perlman: University of Pennsylvania
Noah Burget: University of Pennsylvania
Yeqiao Zhou: University of Pennsylvania
Gregory W. Schwartz: University Health Network
Jelena Petrovic: Genentech
Zora Modrusan: Genentech
Robert B. Faryabi: University of Pennsylvania

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract 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 remain unclear. Here, we systematically identify enhancer-promoter hubs in breast cancer, lymphoma, and leukemia. We find 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 show 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-52375-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52375-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-52375-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().