Mechanisms of gene expression

转录调节是细胞协调单个基因或一组基因表达的手段。最近对单细胞的研究表明，在大多数情况下，转录不是一个连续的活动，而是突然发生的。每个基因产生的RNA数量与这种爆发的幅度和频率成正比。如何控制这两个参数并不完全清楚，但似乎启动子的DNA序列信息决定了振幅，而爆发频率依赖于增强子的序列信息。启动子和增强子也被称为基因调控元件。它们的主要作用是招募酶（聚合酶）和其他关键蛋白质（转录因子、激活剂和抑制剂），这些蛋白质打开DNA螺旋并读取遗传信息。启动子和增强子的另一个重要特征是，要正常发挥作用，它们必须彼此接近或相互接触。本财政年度，我们的实验室探索了细胞如何促进调控DNA之间的接触以驱动转录。

Transcriptional regulation is the means whereby cells orchestrate expression of individual genes or group of genes. Recent studies with single cells have shown that, for the most part, transcription is not a continuous activity but it occurs in bursts. The amount of RNA produced for each gene is directly proportional to the amplitude and frequency of such bursts. How these two parameters are controlled is not totally clear, but it appears that DNA sequence information at promoters determine the amplitude, while burst frequencies rely on sequence information at enhancers. Promoters and enhancers are also known as gene regulatory elements. their primary role is to recruit enzymes (polymerases) and other key proteins (transcription factors, activators and inhibitors) that open up the DNA helix and read the genetic information. Another important feature of promoters and enhancers is that to function properly they must either be in close proximity or in contact with each other. This fiscal year, our laboratory has explored how the cell facilitate contacts between regulatory DNA to drive transcription. Our key publication in this area: 1- El Khattabi et al. Cell, August 2019. In this manuscript we have shown that a large complex known as Mediator recruits RNA polymerases to gene promoters in mammalian cells. Once at promoters, Mediator undergoes a drastic structural change (probably by associating with transcription factors) which in yeast drives phosphorylation of polymerases, an activity essential for transcription. Finally, contrary to current models, we have found that Mediator is not required for the tethering of promoters and enhancers. The new findings therefore shed light on how transcription is regulated in higher organisms.