Vitale Emanuele, Gugnoni Mila, Ciarrocchi Alessia
Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42123 Reggio Emilia, Italy.
Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Via Università 4, 41121 Modena, Italy.
Cancers (Basel). 2021 Oct 16;13(20):5201. doi: 10.3390/cancers13205201.
The control of gene expression at a transcriptional level requires a widespread landscape of regulatory elements. Central to these regulatory circuits are enhancers (ENHs), which are defined as cis-acting DNA elements able to increase the transcription of a target gene in a distance- and orientation-independent manner. ENHs are not independent functional elements but work in a complex and dynamic cooperative network, constituting the building blocks of multimodular domains of gene expression regulation. The information from each of these elements converges on the target promoter, contributing to improving the precision and sharpness of gene modulation. ENHs' interplay varies in its nature and extent, ranging from an additive to redundant effect depending on contexts. Moving from super-enhancers that drive the high expression levels of identity genes, to shadow-enhancers, whose redundant functions contribute to buffering the variation in gene expression, this review aims to describe the different modalities of ENHs' interaction and their role in the regulation of complex biological processes like cancer development.
转录水平上的基因表达调控需要广泛的调控元件景观。这些调控回路的核心是增强子（ENHs），增强子被定义为能够以距离和方向独立的方式增加靶基因转录的顺式作用DNA元件。增强子不是独立的功能元件，而是在一个复杂且动态的协同网络中发挥作用，构成了基因表达调控多模块结构域的组成部分。来自这些元件中每个元件的信息汇聚到靶启动子上，有助于提高基因调控的精度和清晰度。增强子之间的相互作用在性质和程度上各不相同，根据具体情况，其影响范围从累加效应到冗余效应。从驱动身份基因高表达水平的超级增强子，到其冗余功能有助于缓冲基因表达变化的影子增强子，本综述旨在描述增强子相互作用的不同模式及其在癌症发展等复杂生物学过程调控中的作用。
