Casadesús Josep, Low David
Departamento de Genética, Universidad de Sevilla, Seville 41080, Spain.
Microbiol Mol Biol Rev. 2006 Sep;70(3):830-56. doi: 10.1128/MMBR.00016-06.
Like many eukaryotes, bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. Unlike eukaryotes, however, bacteria use DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine methylation plays roles in the virulence of diverse pathogens of humans and livestock animals, including pathogenic Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus, and Brucella. In Alphaproteobacteria, methylation of adenine at GANTC sites by the CcrM methylase regulates the cell cycle and couples gene transcription to DNA replication. In Gammaproteobacteria, adenine methylation at GATC sites by the Dam methylase provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage genomes, transposase activity, and regulation of gene expression. Transcriptional repression by Dam methylation appears to be more common than transcriptional activation. Certain promoters are active only during the hemimethylation interval that follows DNA replication; repression is restored when the newly synthesized DNA strand is methylated. In the E. coli genome, however, methylation of specific GATC sites can be blocked by cognate DNA binding proteins. Blockage of GATC methylation beyond cell division permits transmission of DNA methylation patterns to daughter cells and can give rise to distinct epigenetic states, each propagated by a positive feedback loop. Switching between alternative DNA methylation patterns can split clonal bacterial populations into epigenetic lineages in a manner reminiscent of eukaryotic cell differentiation. Inheritance of self-propagating DNA methylation patterns governs phase variation in the E. coli pap operon, the agn43 gene, and other loci encoding virulence-related cell surface functions.
与许多真核生物一样，细菌广泛利用复制后DNA甲基化来对DNA - 蛋白质相互作用进行表观遗传控制。然而，与真核生物不同的是，细菌使用DNA腺嘌呤甲基化（而非DNA胞嘧啶甲基化）作为表观遗传信号。DNA腺嘌呤甲基化在人类和家畜的多种病原体的毒力中发挥作用，包括致病性大肠杆菌、沙门氏菌、弧菌、耶尔森氏菌、嗜血杆菌和布鲁氏菌。在α - 变形杆菌中，CcrM甲基ase对GANTC位点的腺嘌呤甲基化调节细胞周期，并将基因转录与DNA复制耦合。在γ - 变形杆菌中，Dam甲基ase对GATC位点的腺嘌呤甲基化提供DNA复制、染色体分离、错配修复、噬菌体基因组包装、转座酶活性和基因表达调控的信号。Dam甲基化引起的转录抑制似乎比转录激活更为常见。某些启动子仅在DNA复制后的半甲基化间隔期间活跃；当新合成的DNA链甲基化时，抑制恢复。然而，在大肠杆菌基因组中，特定GATC位点的甲基化可被同源DNA结合蛋白阻断。细胞分裂后GATC甲基化的阻断允许DNA甲基化模式传递给子细胞，并可产生不同的表观遗传状态，每种状态通过正反馈环进行传播。在不同的DNA甲基化模式之间切换可以将克隆细菌群体分裂成表观遗传谱系，其方式类似于真核细胞分化。自我传播的DNA甲基化模式的遗传控制大肠杆菌菌毛操纵子、agn43基因和其他编码与毒力相关的细胞表面功能的基因座中的相变。
