The mechanism by which DNA adenine methylase and papl activate the pap epigenetic switch

被引:100
作者
Hernday, AD [1 ]
Braaten, BA [1 ]
Low, DA [1 ]
机构
[1] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA
关键词
D O I
10.1016/S1097-2765(03)00383-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:947 / 957
页数:11
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