癌症中的空间启动子-增强子枢纽：组织、调控和功能。
Spatial promoter-enhancer hubs in cancer: organization, regulation, and function.
机构信息
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
出版信息
Trends Cancer. 2023 Dec;9(12):1069-1084. doi: 10.1016/j.trecan.2023.07.017. Epub 2023 Aug 19.
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.
转录失调是癌症的一个标志，可能是由增强子景观的改变所驱动的。最近在基因组组织方面的研究表明，多个增强子和启动子可以在空间上聚集在一起，形成动态的拓扑组装，称为启动子-增强子枢纽，它们与基因表达的升高强烈相关。在这篇综述中，我们讨论了在多种癌症类型中最近发现的启动子-增强子枢纽的结构和复杂性。我们进一步讨论了驱动启动子-增强子枢纽失调的潜在机制，并推测了它们在发病机制中的功能作用。了解启动子-增强子枢纽在转录失调中的作用，可以为针对基因组组织的这些复杂特征的新的治疗方法提供深入了解。
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