Histone H3 Lysine 4 Methylation Marks Postreplicative Human Cytomegalovirus Chromatin
Histone H3 Lysine 4 Methylation Marks Postreplicative Human Cytomegalovirus Chromatin
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DOI：
10.1128/jvi.00581-12
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发表时间：
2012-07
影响因子：
5.4
通讯作者：
Alexandra Nitzsche;Charlotte Steinhäusser;Katrin Mücke;C. Paulus;M. Nevels
中科院分区：
文献类型：
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作者：
Alexandra Nitzsche;Charlotte Steinhäusser;Katrin Mücke;C. Paulus;M. Nevels
摘要 在允许细胞的细胞核中，人类巨细胞病毒基因组形成最初类似于异染色质的核小体结构，但逐渐转变为类常染色质状态。这种开关的特点是病毒基因组中组蛋白 H3 K9 甲基化减少，H3 尾部乙酰化和 H3 K4 甲基化显着增加。我们使用更昔洛韦和编码可逆不稳定 DNA 聚合酶的突变病毒来检查 DNA 复制对病毒染色质组蛋白修饰动态的影响。 H3 尾部乙酰化和 H3 K9 甲基化的变化以 DNA 复制独立的方式进行。相比之下，H3 K4 甲基化的增加被证明广泛依赖于病毒 DNA 合成。一致的是，使用“点击化学”标记新生 DNA 表明，在 DNA 复制期间或之后，甲基化 H3 K4 优先掺入病毒（而非细胞）染色质中。这项研究证明了复制后人类巨细胞病毒染色质的选择性表观遗传标记。
ABSTRACT In the nuclei of permissive cells, human cytomegalovirus genomes form nucleosomal structures initially resembling heterochromatin but gradually switching to a euchromatin-like state. This switch is characterized by a decrease in histone H3 K9 methylation and a marked increase in H3 tail acetylation and H3 K4 methylation across the viral genome. We used ganciclovir and a mutant virus encoding a reversibly destabilized DNA polymerase to examine the impact of DNA replication on histone modification dynamics at the viral chromatin. The changes in H3 tail acetylation and H3 K9 methylation proceeded in a DNA replication-independent fashion. In contrast, the increase in H3 K4 methylation proved to depend widely on viral DNA synthesis. Consistently, labeling of nascent DNA using “click chemistry” revealed preferential incorporation of methylated H3 K4 into viral (but not cellular) chromatin during or following DNA replication. This study demonstrates largely selective epigenetic tagging of postreplicative human cytomegalovirus chromatin.