Methylome diversification through changes in DNA methyltransferase sequence specificity.
Methylome diversification through changes in DNA methyltransferase sequence specificity.
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DOI：
10.1371/journal.pgen.1004272
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发表时间：
2014-04
期刊：
影响因子：
4.5
通讯作者：
Kobayashi I
中科院分区：
文献类型：
--
作者：
Furuta Y;Namba-Fukuyo H;Shibata TF;Nishiyama T;Shigenobu S;Suzuki Y;Sugano S;Hasebe M;Kobayashi I
表观遗传修饰如DNA甲基化对基因表达和基因组维持有很大影响。幽门螺杆菌是一种人类胃部致病菌，具有大量的DNA甲基转移酶基因，不同菌株具有独特的基因库。以前的基因组比较表明，这些甲基转移酶经常改变DNA序列的特异性，通过域移动-运动之间和目标识别域的编码序列的基因内。使用单分子实时测序技术，检测N6-甲基腺嘌呤和N4-甲基胞嘧啶与单碱基分辨率，我们研究了甲基化的DNA位点整个H。pylori基因组的几个密切相关的菌株。总体而言，甲基化组在密切相关的菌株中高度可变。例如，在RNA聚合酶的rpoB基因中发现了高甲基化区域。我们确定了甲基化的DNA序列基序，然后将它们中的每一个分配给I型和其他限制修饰系统的特异性决定基因中的靶识别结构域的特定同源组。这些结果支持DNA甲基转移酶序列特异性变化的机制。敲除其中一个I型特异性基因导致转录组变化，这表明其在基因表达中的作用。这些结果与DNA甲基化驱动的进化概念一致，其中甲基化组的变化导致转录组的变化，并可能导致表型的变化，为自然或人工选择提供目标。除了DNA序列变异之外，生物体还受到表观遗传变异的影响。DNA甲基化是原核生物和真核生物中研究最多的表观遗传修饰之一。在原核生物中，大多数DNA甲基化是通过具有高序列特异性的DNA甲基转移酶进行的。幽门螺杆菌是一种导致胃癌和其他疾病的人类胃病原体，携带大量DNA甲基转移酶基因，这些基因在菌株之间存在差异。在这项工作中，我们研究了DNA甲基化在多个H。pylori基因组使用单分子实时测序技术，检测DNA甲基化与单碱基分辨率。比较密切相关的基因组之间的甲基化基序允许分配识别序列到每个DNA甲基化特异性决定基因。高度甲基化的基因被检测到，虽然一般的DNA甲基化模式不同菌株。甲基化特异性决定基因的敲除导致转录组的变化。这些发现与我们的假设一致，即甲基化组的变化导致转录组的变化和表型的变化，为适应性进化中的自然选择和人工选择提供了潜在的目标。
Epigenetic modifications such as DNA methylation have large effects on gene expression and genome maintenance. Helicobacter pylori, a human gastric pathogen, has a large number of DNA methyltransferase genes, with different strains having unique repertoires. Previous genome comparisons suggested that these methyltransferases often change DNA sequence specificity through domain movement—the movement between and within genes of coding sequences of target recognition domains. Using single-molecule real-time sequencing technology, which detects N6-methyladenines and N4-methylcytosines with single-base resolution, we studied methylated DNA sites throughout the H. pylori genome for several closely related strains. Overall, the methylome was highly variable among closely related strains. Hypermethylated regions were found, for example, in rpoB gene for RNA polymerase. We identified DNA sequence motifs for methylation and then assigned each of them to a specific homology group of the target recognition domains in the specificity-determining genes for Type I and other restriction-modification systems. These results supported proposed mechanisms for sequence-specificity changes in DNA methyltransferases. Knocking out one of the Type I specificity genes led to transcriptome changes, which suggested its role in gene expression. These results are consistent with the concept of evolution driven by DNA methylation, in which changes in the methylome lead to changes in the transcriptome and potentially to changes in phenotype, providing targets for natural or artificial selection. Living organisms are affected by epigenetic variation in addition to DNA sequence variation. DNA methylation is one of the most studied epigenetic modifications in both prokaryotes and eukaryotes. In prokaryotes, most DNA methylation is by DNA methyltransferases with high sequence specificity. Helicobacter pylori, a human stomach pathogen responsible for stomach cancer and other diseases, carries a large number of DNA methyltransferase genes that vary among strains. In this work, we examined the distribution of DNA methylation in multiple H. pylori genomes using single-molecule real-time sequencing technology, which detects DNA methylation with single-base resolution. Comparison of methylation motifs between closely related genomes allowed assignment of a recognition sequence to each DNA methylation specificity-determining gene. Highly methylated genes were detected, although the general DNA methylation pattern varied among strains. Knockout of a methylation specificity-determining gene led to changes in the transcriptome. These findings are consistent with our hypothesis that changes in the methylome lead to changes in the transcriptome and to changes in phenotypes, providing potential targets for natural and artificial selection in adaptive evolution.
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比较幽门螺杆菌临床菌株UM032和小鼠适应的衍生物的基因组。
影响因子：
4.2
作者：
Khosravi Y;Rehvathy V;Wee WY;Wang S;Baybayan P;Singh S;Ashby M;Ong J;Amoyo AA;Seow SW;Choo SW;Perkins T;Chua EG;Tay A;Marshall BJ;Loke MF;Goh KL;Pettersson S;Vadivelu J
通讯作者：
Vadivelu J
影响因子：
48
作者：
Flusberg, Benjamin A.;Webster, Dale R.;Lee, Jessica H.;Travers, Kevin J.;Olivares, Eric C.;Clark, Tyson A.;Korlach, Jonas;Turner, Stephen W.
通讯作者：
Turner, Stephen W.
DOI：
10.1007/s004380050677
发表时间：
1998-03-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
Heuermann, D;Haas, R
通讯作者：
Haas, R
DOI：
10.1073/pnas.1012579108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Furuta, Yoshikazu;Kawai, Mikihiko;Kobayashi, Ichizo
通讯作者：
Kobayashi, Ichizo
影响因子：
9.2
作者：
Kato, M;Miura, A;Kakutani, T
通讯作者：
Kakutani, T