Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Universidad de Buenos Aires-CONICET, Buenos Aires 1428, Argentina.
Department of Genetics and Developmental Biology, The Rappaport Faculty of Medicine and Research Institute, Technion - Israel Institute of Technology, Haifa 3109601, Israel.
Trends Genet. 2019 Jun;35(6):423-433. doi: 10.1016/j.tig.2019.03.006. Epub 2019 Apr 18.
The current paradigm in the field of gene regulation postulates that regulatory information for generating gene expression is organized into modules (enhancers), each containing the information for driving gene expression in a single spatiotemporal context. This modular organization is thought to facilitate the evolution of gene expression by minimizing pleiotropic effects. Here we review recent studies that provide evidence of quite the opposite: (i) enhancers can function in multiple developmental contexts, implying that enhancers can be pleiotropic, (ii) transcription factor binding sites within pleiotropic enhancers are reused in different contexts, and (iii) pleiotropy impacts the structure and evolution of enhancers. Altogether, this evidence suggests that enhancer pleiotropy is pervasive in animal genomes, challenging the commonly held view of modularity.
目前，基因调控领域的范式假定，生成基因表达的调控信息被组织成模块（增强子），每个模块包含在单个时空背景下驱动基因表达的信息。这种模块化组织被认为通过最小化多效性效应来促进基因表达的进化。在这里，我们回顾了最近的研究，这些研究提供了相反的证据：（i）增强子可以在多个发育背景中发挥作用，这意味着增强子可以是多效性的，（ii）多效性增强子中的转录因子结合位点在不同的背景中被重复使用，以及（iii）多效性影响增强子的结构和进化。总的来说，这些证据表明，增强子的多效性在动物基因组中普遍存在，挑战了模块化的普遍观点。
