The mechanism by which DNA adenine methylase and papl activate the pap epigenetic switch
The mechanism by which DNA adenine methylase and papl activate the pap epigenetic switch
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DOI：
10.1016/s1097-2765(03)00383-6
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发表时间：
2003-10-01
期刊：
影响因子：
16
通讯作者：
Low, DA
中科院分区：
文献类型：
--
作者：
Hernday, AD;Braaten, BA;Low, DA
肾盂肾炎相关皮利（Pap）在尿路致病性大肠杆菌中的表达受一个可逆的OFF到ON开关的表观遗传学控制。在相关闭的细胞中，全局调节Lrp结合到接近菌毛蛋白启动子的pap位点，而在相打开的细胞中，Lrp结合到启动子远端位点。我们已经发现，局部调节因子Papl增加了Lrp对序列“ACGATC”的亲和力，该序列包含DNA腺嘌呤甲基化酶（Dam）的靶“GATC”位点，并且存在于启动子近端和远端位点中。突变分析表明，甲基化的启动子近端GATC（prox）网站的大坝是必要的过渡到相位ON状态，通过特异性阻断Papl依赖性结合Lrp启动子近端网站。此外，我们的数据支持这样的假设，即Papl依赖性结合Lrp的半甲基化的GATC（dist）网站产生的DNA复制是一个关键组成部分的开关机制。
The expression of pyelonephritis-associated pili (Pap) in uropathogenic Escherichia coli is epigenetically controlled by a reversible OFF to ON switch. In phase OFF cells, the global regulator Lrp is bound to pap sites proximal to the pilin promoter, whereas in phase ON cells, Lrp is bound to promoter distal sites. We have found that the local regulator Papl increases the affinity of Lrp for the sequence "ACGATC," which contains the target "GATC" site for DNA adenine methylase (Dam) and is present in both promoter proximal and distal sites. Mutational analyses show that methylation of the promoter proximal GATC(prox) site by Dam is required for transition to the phase ON state by specifically blocking Papl-dependent binding of Lrp to promoter proximal sites. Furthermore, our data support the hypothesis that Papl-dependent binding of Lrp to a hemimethylated GATC(dist) site generated by DNA replication is a critical component of the switch mechanism.