Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, 40126 Bologna, Italy.
Nucleic Acids Res. 2014 Mar;42(5):3138-51. doi: 10.1093/nar/gkt1258. Epub 2013 Dec 9.
Most transcriptional regulators bind nucleotide motifs in the major groove, although some are able to recognize molecular determinants conferred by the minor groove of DNA. Here we report a transcriptional commutator switch that exploits the alternative readout of grooves to mediate opposite output regulation for the same input signal. This mechanism accounts for the ability of the Helicobacter pylori Fur regulator to repress the expression of both iron-inducible and iron-repressible genes. When iron is scarce, Fur binds to DNA as a dimer, through the readout of thymine pairs in the major groove, repressing iron-inducible transcription (FeON). Conversely, on iron-repressible elements the metal ion acts as corepressor, inducing Fur multimerization with consequent minor groove readout of AT-rich inverted repeats (FeOFF). Our results provide first evidence for a novel regulatory paradigm, in which the discriminative readout of DNA grooves enables to toggle between the repression of genes in a mutually exclusive manner.
大多数转录调节剂结合在 DNA 大沟中的核苷酸基序，尽管有些调节剂能够识别 DNA 小沟赋予的分子决定因素。在这里，我们报告了一种转录换向开关，它利用沟的替代读取来介导相同输入信号的相反输出调节。这种机制解释了幽门螺杆菌 Fur 调节剂能够抑制铁诱导和铁抑制基因表达的能力。当铁缺乏时，Fur 通过读取大沟中的胸腺嘧啶对作为二聚体结合 DNA，从而抑制铁诱导的转录（FeON）。相反，在铁抑制元件上，金属离子作为辅助阻遏物，诱导 Fur 多聚化，从而导致富含 AT 的反向重复（FeOFF）的小沟读取。我们的结果为一种新的调控范例提供了第一个证据，其中 DNA 沟的区分读取能够以相互排斥的方式在基因的抑制之间进行切换。
