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Review
. 2023 Dec;9(12):1069-1084.
doi: 10.1016/j.trecan.2023.07.017. Epub 2023 Aug 19.

Spatial promoter-enhancer hubs in cancer: organization, regulation, and function

Jingru Zhao  1 , Robert B Faryabi  2
Affiliations
Review

Spatial promoter-enhancer hubs in cancer: organization, regulation, and function

Jingru Zhao et al. Trends Cancer. 2023 Dec.

Abstract

Transcriptional dysregulation is a hallmark of cancer and can be driven by altered enhancer landscapes. Recent studies in genome organization have revealed that multiple enhancers and promoters can spatially coalesce to form dynamic topological assemblies, known as promoter-enhancer hubs, which strongly correlate with elevated gene expression. In this review, we discuss the structure and complexity of promoter-enhancer hubs recently identified in multiple cancer types. We further discuss underlying mechanisms driving dysregulation of promoter-enhancer hubs and speculate on their functional role in pathogenesis. Understanding the role of promoter-enhancer hubs in transcriptional dysregulation can provide insight into new therapeutic approaches to target these complex features of genome organization.

Keywords: cancer; multiway interaction; promoter–enhancer hub.

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Conflict of interest statement

Declaration of interests None declared by authors.

Figures

Figure 1:
Figure 1:. Graphical representation of promoter–enhancer hubs linearly and spatially.
Top: one promoter regulated by two enhancers. Bottom: two promoters that are regulated by two enhancers.
Figure 2:
Figure 2:. Evidence suggests that multiway interactions among enhancers and promoters are dynamic.
Hence, a promoter may be interacting with one, both, or none of its enhancers at a given time.
Figure 3:
Figure 3:. Various assays offer different perspectives of enhancer–promoter interactions.
Top: five nuclei depicting two alleles that contain a promoter (green), and two enhancers (blue and yellow). Bottom-left: DNA-FISH-based assays can be used to measure pairwise and multiway interactions at individual alleles of a given locus. Bottom-right: Hi-C-based assays cannot measure multiway interactions but can be used to find highly connected promoter–enhancer pairs genome-wide.
Figure 4:
Figure 4:. Example of events influencing oncogenic promoter–enhancer hubs.
Top-left: changes in binding of one TF can activate previously inactive enhancers and recruit other partner TFs. Top-right: Genetic alterations can create novel binding sites for TFs and alter enhancer activity, inducing gene expression. Bottom: loss of insulation can lead to de novo contacts to enhancers.
See this image and copyright information in PMC

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