增强子调控异常与恶性肿瘤的关系研究进展

Research advances of the correlation between abnormal regulation of enhancer and malignant tumor

增强子是真核生物基因组中一类特殊的转录调控元件,真核生物的基因组中分布着大量增强子元件。增强子可通过形成染色质环结构与靶基因的启动子相互作用,从而与启动子共同调控靶基因的转录。大量研究表明,遗传变异、表观修饰改变及转录因子异常均会直接或间接导致增强子功能失调或基因组增强子重塑,并与恶性肿瘤的发生和恶性进展密切相关。近年来高通量测序技术和数据库的快速发展有力推进了增强子研究的深度和广度。本文对增强子的结构特征、调控模式,及其在肿瘤发生和发展过程中调控异常的形成机制、增强子鉴定的主要技术手段和常用数据库等进行了简要的介绍和概括。

The enhancer is a special class of transcriptional regulatory elements in eukaryotic genomes.There are a large number of enhancer elements in eukaryotic genomes.Enhancers can interact with the promoters of target genes through the formation of chromatin loop,and regulate the transcription of target genes together with the promoters.A large number of studies have shown that genetic variations,epigenetic modifications and abnormal transcription factors can directly or indirectly lead to enhancer dysfunction or genome enhancer remodeling that are closely correlation to the occurrence and progression of malignant tumor.In recent years,the rapid development and update of high⁃throughput sequencing technology and database have strongly enhanced the depth and breadth of enhancer research.In this review,we briefly introduced and summarized the structural characteristics and the regulation mode of enhancers,and the formation mechanism of abnormal regulation in the process of tumorigenesis and development,as well as the main technical means of enhancer identification and common databases.