Department of Molecular, Cellular, and Developmental Biology, the University of Michigan, Ann Arbor, MI 48109-1048, USA.
J Bacteriol. 2010 Oct;192(19):4821-6. doi: 10.1128/JB.00883-09. Epub 2010 Jul 9.
The nitrogen assimilation control protein (NAC) of Klebsiella pneumoniae is a LysR-type transcriptional regulator that activates transcription when bound to a DNA site (ATAA-N5-TnGTAT) centered at a variety of distances from the start of transcription. The NAC-binding site from the hutU promoter (NBShutU) is centered at -64 relative to the start of transcription but can activate the lacZ promoter from sites at -64, -54, -52, and -42 but not from sites at -47 or -59. However, the NBSs from the ureD promoter (ureDp) and codB promoter (codBp) are centered at -47 and -59, respectively, and NAC is fully functional at these promoters. Therefore, we compared the activities of the NBShutU and NBSureD within the context of ureDp as well as within codBp. The NBShutU functioned at both of these sites. The NBSureD has the same asymmetric core as the NBShutU. Inverting the NBSureD abolished more than 99% of NAC's ability to activate ureDp. The key to the activation lies in the TnG segment of the TnGTAT half of the NBSureD. Changing TnG to GnT, TnT, or GnG drastically reduced ureDp activation (to 0.5%, 6%, or 15% of wild-type activation, respectively). The function of the NBSureD, like that of the NBShutU, requires that the TnGTAT half of the NBS be on the promoter-proximal (downstream) side of the NBS. Taken together, our data suggest that the positional specificity of an NBS is dependent on the promoter in question and is more flexible than previously thought, allowing considerable latitude both in distance and on the face of the DNA helix for the NBS relative to that of RNA polymerase.
肺炎克雷伯氏菌的氮同化控制蛋白(NAC)是一种 LysR 型转录调节因子,当与 DNA 结合位点(ATAA-N5-TnGTAT)结合时,该结合位点位于转录起始点的各种距离处,从而激活转录。hutU 启动子的 NAC 结合位点(NBShutU)位于转录起始点的-64 处,但可以从-64、-54、-52 和-42 处的启动子激活 lacZ 启动子,但不能从-47 或-59 处的启动子激活。然而,ureD 启动子(ureDp)和 codB 启动子(codBp)的 NBS 分别位于-47 和-59 处,并且 NAC 在这些启动子上完全发挥功能。因此,我们比较了 NBShutU 和 NBSureD 在 ureDp 中的活性以及在 codBp 中的活性。NBShutU 在这两个位点都发挥作用。NBSureD 具有与 NBShutU 相同的不对称核心。颠倒 NBSureD 会使 NAC 激活 ureDp 的能力丧失 99%以上。激活的关键在于 NBSureD 的 TnGTAT 半部分的 TnG 片段。将 TnG 变为 GnT、TnT 或 GnG 会大大降低 ureDp 的激活(分别为野生型激活的 0.5%、6%或 15%)。与 NBShutU 一样,NBSureD 的功能要求 NBS 的 TnGTAT 半部分位于 NBS 的启动子近端(下游)侧。综上所述,我们的数据表明,NBS 的位置特异性取决于所讨论的启动子,并且比以前认为的更具灵活性,允许 NBS 相对于 RNA 聚合酶在距离和 DNA 螺旋面上具有相当大的自由度。