转录因子的浓度能影响基因表达吗?

Zafer Koşar, A. Erbaş
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引用次数: 5

摘要

DNA是通过基因编码生命的终极分子。沿着一米长的DNA分子定位的基因必须通过严格的调控过程在正确的时间以正确的数量表达。基因的调控始于DNA结合蛋白转录因子(TF)与沿双链DNA分子的靶调控元件的结合。通常,TFs以序列特异性的方式附着在DNA上,可以靶向不同长度的DNA基序,但一些TFs也可以与DNA非特异性相互作用。由此产生的DNA- tf复合物可以通过控制靶DNA序列上RNA聚合酶的募集直接控制基因表达。最近的单分子实验为这种控制模式增加了一个新的维度;DNA- tf复合物的寿命(即蛋白质在其DNA位点上的停留时间)可以作为调控成分发挥作用。这一突破不可避免地表明,任何能够改变dna结合蛋白停留时间的物理化学成分也可能参与基因调控。从这个角度来看,我们认为TF蛋白的细胞浓度可以通过调节蛋白质的dna停留时间来促进细胞尺度的转录活性。细胞可以通过浓度依赖的解离机制或促进多蛋白- dna复合物的形成来实现这一目标。虽然我们在这里的讨论将考虑来自原核细胞的例子,但我们也将简要地指出,类似的机制也可能在真核细胞中起作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Can the Concentration of a Transcription Factor Affect Gene Expression?
DNA is the ultimate molecule that encodes life through genes. Genes positioned along the meter-long DNA molecule have to be expressed at the right time and in the right amount via strict regulatory processes. Regulation of a gene starts with the binding of a DNA-binding protein known as a transcription factor (TF) to a target regulatory element along the double-stranded DNA molecule. Often, TFs attach to DNA in a sequence-specific manner and can target DNA motifs of various lengths, yet some TFs can also interact with DNA nonspecifically. The resulting DNA-TF complexes can control gene expression directly via controlling the recruitment of RNA polymerase on the target DNA sequence. Recent single-molecule experiments have added a new dimension to such control mode; the lifetime of a DNA-TF complex (i.e., the residence time of the protein on its DNA site) can function as a regulatory component. This breakthrough inevitably suggests that any physiochemical constituent that can alter the residence time of a DNA-binding protein can also be involved in gene regulation. In this perspective, we argue that a TF protein’s cellular concentration can contribute to the cell-scale transcription activity by modulating the DNA-residence time of the protein. Cells can achieve this either by enabling a concentration-dependent dissociation mechanism or by promoting the formation of multiprotein-DNA complexes. While our discussion here will consider examples from prokaryotic cells, we will also briefly argue that similar mechanisms could also be functional in eukaryotic cells.
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