Detailed analysis of Helicobacter pylori Fur-regulated promoters reveals a Fur box core sequence and novel Fur-regulated genes.
Detailed analysis of Helicobacter pylori Fur-regulated promoters reveals a Fur box core sequence and novel Fur-regulated genes.
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DOI：
10.1111/j.1365-2958.2012.08066.x
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发表时间：
2012-06
影响因子：
3.6
通讯作者：
Merrell DS
中科院分区：
文献类型：
--
作者：
Pich OQ;Carpenter BM;Gilbreath JJ;Merrell DS
在幽门螺杆菌中，铁的平衡由铁摄取调节蛋白(Fur)控制，Fur是一种铁敏感的阻遏蛋白，通常调节与铁的运输和储存有关的基因的表达。在这里，我们对Fur调控的启动子进行了广泛的分析，并确定了一个具有二联体对称性的7-1-7基序(5‘-TAATAATnATTATTA-3’)，它是幽门螺杆菌的Fur box核心序列。将该序列添加到典型的非毛发调控基因的启动子区域，足以在体内实施毛发依赖的调控。此外，Fur控制的启动子中该序列的突变否定了调控。幽门螺杆菌染色体对Fur box的分析证实了在许多已知的Fur调控基因的启动子中存在保守的Fur盒，并揭示了新的Fur靶标。对新的候选基因的转录分析表明，HPG27_51、HPG27_52、HPG27_199、HPG27_445、HPG27_825和HPG27_1063的转录依赖于Fur的抑制，以及Fur介导的细胞毒素相关基因cagA(HPG27_507)的激活。此外，电泳迁移率改变分析证实了Fur与每个基因的启动子的特异性结合。未来的实验将确定这些特定基因中任何一个毛皮调控的缺失是否会导致幽门螺杆菌毛皮突变体表现出的定植缺陷。
In Helicobacter pylori, iron balance is controlled by the Ferric uptake regulator (Fur), an iron-sensing repressor protein that typically regulates expression of genes implicated in iron transport and storage. Herein, we carried out extensive analysis of Fur-regulated promoters and identified a 7-1-7 motif with dyad symmetry (5’-TAATAATnATTATTA-3’), which functions as the Fur box core sequence of H. pylori. Addition of this sequence to the promoter region of a typically non-Fur regulated gene was sufficient to impose Fur-dependent regulation in vivo. Moreover, mutation of this sequence within Fur-controlled promoters negated regulation. Analysis of the H. pylori chromosome for the occurrence of the Fur box established the existence of well-conserved Fur-boxes in the promoters of numerous known Fur-regulated genes, and revealed novel putative Fur targets. Transcriptional analysis of the new candidate genes demonstrated Fur-dependent repression of HPG27_51, HPG27_52, HPG27_199, HPG27_445, HPG27_825 and HPG27_1063, as well as Fur-mediated activation of the cytotoxin associated gene A, cagA (HPG27_507). Furthermore, electrophoretic mobility shift assays confirmed specific binding of Fur to the promoters of each of these genes. Future experiments will determine whether loss of Fur regulation of any of these particular genes contributes to the defects in colonization exhibited by the H. pylori fur mutant.
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影响因子：
14.9
作者：
Chen Z;Lewis KA;Shultzaberger RK;Lyakhov IG;Zheng M;Doan B;Storz G;Schneider TD
通讯作者：
Schneider TD
影响因子：
3.2
作者：
Beier, D;Spohn, G;Scarlato, V
通讯作者：
Scarlato, V
影响因子：
3.6
作者：
Bsat, N;Herbig, A;Helmann, JD
通讯作者：
Helmann, JD
影响因子：
3.2
作者：
CALDERWOOD, SB;MEKALANOS, JJ
通讯作者：
MEKALANOS, JJ
DOI：
10.1073/pnas.0404817101
发表时间：
2004-11-30
影响因子：
11.1
作者：
Bäckström, A;Lundberg, C;Arnqvist, A
通讯作者：
Arnqvist, A