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评估增强子功能和转录。

Evaluating Enhancer Function and Transcription.

机构信息

Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, USA; email:

出版信息

Annu Rev Biochem. 2020 Jun 20;89:213-234. doi: 10.1146/annurev-biochem-011420-095916. Epub 2020 Mar 20.

Abstract

Cell-type- and condition-specific profiles of gene expression require coordination between protein-coding gene promoters and -regulatory sequences called enhancers. Enhancers can stimulate gene activity at great genomic distances from their targets, raising questions about how enhancers communicate with specific gene promoters and what molecular mechanisms underlie enhancer function. Characterization of enhancer loci has identified the molecular features of active enhancers that accompany the binding of transcription factors and local opening of chromatin. These characteristics include coactivator recruitment, histone modifications, and noncoding RNA transcription. However, it remains unclear which of these features functionally contribute to enhancer activity. Here, we discuss what is known about how enhancers regulate their target genes and how enhancers and promoters communicate. Further, we describe recent data demonstrating many similarities between enhancers and the gene promoters they control, and we highlight unanswered questions in the field, such as the potential roles of transcription at enhancers.

摘要

细胞类型和条件特异性基因表达谱需要蛋白质编码基因启动子和称为增强子的调节序列之间的协调。增强子可以在与其靶基因的巨大基因组距离处刺激基因活性,这引发了关于增强子如何与特定基因启动子进行通信以及增强子功能的基础分子机制的问题。增强子基因座的特征描述了与转录因子结合和局部染色质开放相关的活性增强子的分子特征。这些特征包括共激活因子募集、组蛋白修饰和非编码 RNA 转录。然而,目前尚不清楚这些特征中哪些具有促进增强子活性的功能。在这里,我们讨论了增强子如何调节其靶基因以及增强子和启动子如何进行通信。此外,我们描述了最近的数据,这些数据表明增强子和它们所控制的基因启动子之间有许多相似之处,并强调了该领域尚未解决的问题,例如转录在增强子中的潜在作用。

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