ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, ACT 2600, Canberra City, Australia.
School of Biomedical Sciences, University of Melbourne, 3010, Parkville, Australia.
Bioessays. 2018 Apr;40(4):e1700235. doi: 10.1002/bies.201700235. Epub 2018 Mar 5.
Emerging evidence suggests that DNA topology plays an instructive role in cell fate control through regulation of gene expression. Transcription produces torsional stress, and the resultant supercoiling of the DNA molecule generates an array of secondary structures. In turn, local DNA architecture is harnessed by the cell, acting within sensory feedback mechanisms to mediate transcriptional output. MYC is a potent oncogene, which is upregulated in the majority of cancers; thus numerous studies have focused on detailed understanding of its regulation. Dissection of regulatory regions within the MYC promoter provided the first hint that intimate feedback between DNA topology and associated DNA remodeling proteins is critical for moderating transcription. As evidence of such regulation is also found in the context of many other genes, here we expand on the prototypical example of the MYC promoter, and also explore DNA architecture in a genome-wide context as a global mechanism of transcriptional control.
新兴证据表明，DNA 拓扑结构通过调节基因表达在细胞命运控制中起着指导作用。转录产生扭转应力，导致 DNA 分子的超螺旋化产生一系列二级结构。反过来，局部 DNA 结构被细胞利用，在感应反馈机制中发挥作用，从而调节转录输出。MYC 是一种有效的致癌基因，在大多数癌症中上调；因此，许多研究都集中在对其调控的详细了解上。对 MYC 启动子内的调控区域进行剖析，首次提示 DNA 拓扑结构与相关 DNA 重塑蛋白之间的紧密反馈对于调节转录至关重要。由于在许多其他基因的背景下也发现了这种调控的证据，因此在这里我们扩展了 MYC 启动子的典型范例，并在全基因组范围内探索 DNA 结构作为转录控制的全局机制。
