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Enhancer–promoter specificity in gene transcription: molecular mechanisms and disease associations
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Enhancer–promoter specificity in gene transcription: molecular mechanisms and disease associations
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Journal Article
Enhancer–promoter specificity in gene transcription: molecular mechanisms and disease associations
2024
Overview
Although often located at a distance from their target gene promoters, enhancers are the primary genomic determinants of temporal and spatial transcriptional specificity in metazoans. Since the discovery of the first enhancer element in simian virus 40, there has been substantial interest in unraveling the mechanism(s) by which enhancers communicate with their partner promoters to ensure proper gene expression. These research efforts have benefited considerably from the application of increasingly sophisticated sequencing- and imaging-based approaches in conjunction with innovative (epi)genome-editing technologies; however, despite various proposed models, the principles of enhancer–promoter interaction have still not been fully elucidated. In this review, we provide an overview of recent progress in the eukaryotic gene transcription field pertaining to enhancer–promoter specificity. A better understanding of the mechanistic basis of lineage- and context-dependent enhancer–promoter engagement, along with the continued identification of functional enhancers, will provide key insights into the spatiotemporal control of gene expression that can reveal therapeutic opportunities for a range of enhancer-related diseases.
Enhancers in focus: insights into spatiotemporal gene expression control
This review summarizes the current understanding of enhancer-promoter interactions (EPIs), a key feature of genome structure, in gene regulation and disease. EPIs are crucial for proper gene activity, and their alteration by mutational events can be pathological, causing, among others, cancer, and neurodevelopmental disorders. The authors provide an overview of various methods used to study 3D genome architecture (the physical structure of chromosomes) and discuss recent insights that these techniques have afforded, especially with regard to the specificity and dynamics of EPIs as well as the underlying molecular mechanisms. The review highlights the broad experimental utility of CRISPR-based strategies and their therapeutic potential for targeting disease-related EPIs. While substantial progress has been made, further elucidation of the physical and functional interplay of enhancers with their cognate promoter(s) will reveal new treatment opportunities for many diseases.
This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
