AI Article Synopsis
- - Researchers mapped out interactions between regulatory elements in cancer cells, focusing on promoter-enhancer hubs that play a role in gene expression but whose details remain unclear.
- - By combining genomics, transcription factor screening, and optical mapping, they identified important promoter-enhancer hubs in triple negative breast cancer (TNBC) and studied their variations and regulators.
- - Their findings indicate that these hubs are dynamic and influenced by specific transcription factors (like SOX9 and NOTCH1), helping to tailor gene expression to different cancer subtypes.
Article Abstract
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 and 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 and 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305386 | PMC |
| http://dx.doi.org/10.1126/sciadv.adl4043 | DOI Listing |
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