Haemophilus influenzae phasevarions have evolved from type III DNA restriction systems into epigenetic regulators of gene expression.
Haemophilus influenzae phasevarions have evolved from type III DNA restriction systems into epigenetic regulators of gene expression.
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流感嗜血杆菌的相变已从III型DNA限制系统演变为基因表达的表观遗传调节剂。
DOI：
10.1093/nar/gkm571
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发表时间：
2007
影响因子：
14.9
通讯作者：
Jennings MP
中科院分区：
文献类型：
--
作者：
Fox KL;Dowideit SJ;Erwin AL;Srikhanta YN;Smith AL;Jennings MP
已经在多种病原性细菌中鉴定了与III型限制修饰（R-M）系统相关的阶段性表达（随机转换）甲基转移酶。我们以前已经表明，相可变甲基转移酶（Mod）与流感嗜血杆菌菌株Rd中的III型R-M系统相关联，协调多个基因表达的随机切换，并构成相可变调节子-“相可变”。我们现在已经确定了在H.流感病毒Rd株为5′-CGAAT-3′。这是与先前描述的HinfIII系统相同的识别位点。对59株H.流感病毒株在与靶位点识别相关的MOD基因的中央可变区显示出显著的序列异质性。使用Mod甲基化或非甲基化质粒的菌株内和菌株间转化实验以及甲基化位点测定证明，在编码靶位点特异性的区域中观察到的序列异质性确实与不同的靶位点相关。在所调查的几种菌株中鉴定出res基因内的突变，表明Res不起作用。这些数据表明，这种III型R-M系统进化为控制基因表达的表观遗传机制，在某些菌株中，导致DNA限制性功能丧失。
Phase variably expressed (randomly switching) methyltransferases associated with type III restriction-modification (R-M) systems have been identified in a variety of pathogenic bacteria. We have previously shown that a phase variable methyltransferase (Mod) associated with a type III R-M system in Haemophilus influenzae strain Rd coordinates the random switching of expression of multiple genes, and constitutes a phase variable regulon—‘phasevarion’. We have now identified the recognition site for the Mod methyltransferase in H. influenzae strain Rd as 5′-CGAAT-3′. This is the same recognition site as the previously described HinfIII system. A survey of 59 H. influenzae strains indicated significant sequence heterogeneity in the central, variable region of the mod gene associated with target site recognition. Intra- and inter-strain transformation experiments using Mod methylated or non-methylated plasmids, and a methylation site assay demonstrated that the sequence heterogeneity seen in the region encoding target site specificity does correlate to distinct target sites. Mutations were identified within the res gene in several strains surveyed indicating that Res is not functional. These data suggest that evolution of this type III R-M system into an epigenetic mechanism for controlling gene expression has, in some strains, resulted in loss of the DNA restriction function.