Levens David, Baranello Laura, Kouzine Fedor
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Biophys Rev. 2016 Nov;8(Suppl 1):23-32. doi: 10.1007/s12551-016-0243-5. Epub 2016 Nov 14.
Transcription initiation is a major control point for the precise regulation of gene expression. Our knowledge of this process has been mainly derived from protein-centric studies wherein cis-regulatory DNA sequences play a passive role, mainly in arranging the protein machinery to coalesce at the transcription start sites of genes in a spatial and temporal-specific manner. However, this is a highly dynamic process in which molecular motors such as RNA polymerase II (RNAPII), helicases, and other transcription factors, alter the level of mechanical force in DNA, rather than simply a set of static DNA-protein interactions. The double helix is a fiber that responds to flexural and torsional stress, which if accumulated, can affect promoter output as well as change DNA and chromatin structure. The relationship between DNA mechanics and the control of early transcription initiation events has been under-investigated. Genomic techniques to display topological stress and conformational variation in DNA across the mammalian genome provide an exciting new insight on the role of DNA mechanics in the early stages of the transcription cycle. Without understanding how torsional and flexural stresses are generated, transmitted, and dissipated, no model of transcription will be complete and accurate.
转录起始是基因表达精确调控的主要控制点。我们对这一过程的了解主要源于以蛋白质为中心的研究，在这些研究中，顺式调控DNA序列起着被动作用，主要是将蛋白质机器以时空特异性方式聚集在基因的转录起始位点。然而，这是一个高度动态的过程，其中诸如RNA聚合酶II（RNAPII）、解旋酶和其他转录因子等分子马达会改变DNA中的机械力水平，而不仅仅是一组静态的DNA-蛋白质相互作用。双螺旋是一种对弯曲和扭转应力有反应的纤维，如果这种应力积累起来，会影响启动子输出以及改变DNA和染色质结构。DNA力学与早期转录起始事件控制之间的关系一直未得到充分研究。显示哺乳动物基因组中DNA拓扑应力和构象变化的基因组技术为DNA力学在转录周期早期阶段的作用提供了令人兴奋的新见解。如果不了解扭转和弯曲应力是如何产生、传递和消散的，任何转录模型都将是不完整和不准确的。
