HIV integration site selection: Analysis by massively parallel pyrosequencing reveals association with epigenetic modifications
HIV integration site selection: Analysis by massively parallel pyrosequencing reveals association with epigenetic modifications
复制标题
DOI：
10.1101/gr.6286907
复制
发表时间：
2007-08-01
期刊：
影响因子：
7
通讯作者：
Bushman, Frederic D.
中科院分区：
文献类型：
--
作者：
Wang, Gary P.;Ciuffi, Angela;Bushman, Frederic D.
逆转录病毒DNA整合到宿主细胞DNA中是逆转录病毒复制的定义特征。已知HIV整合在活性转录单位中是有利的，这促进了病毒基因的有效转录，但负责靶向的分子机制尚未完全阐明。在这里，我们使用焦磷酸测序来绘制40，569个HIV整合的独特位点。靶DNA中的核小体位置的计算预测表明，整合位点周期性地分布在核小体表面上，与染色质中面向外的DNA大沟中的有利整合一致。在密集注释的ENCODE区域中的整合位点位置的分析揭示了整合频率和基因组特征之间的大量新关联。整合在转录相关的组蛋白修饰附近特别有利，包括H3乙酰化，H4乙酰化和H3 K4甲基化，但在富含转录抑制修饰的区域不利，包括H3 K27三甲基化和DNA CpG甲基化。统计建模表明，组蛋白修饰对HIV整合的影响部分独立于影响整合的其他基因组特征。焦磷酸测序和生物信息学的方法，这里描述的应该是有用的调查逆转录病毒DNA整合的许多方面。
Integration of retroviral DNA into host cell DNA is a defining feature of retroviral replication. HIV integration is known to be favored in active transcription units, which promotes efficient transcription of the viral genes, but the molecular mechanisms responsible for targeting are not fully clarified. Here we used pyrosequencing to map 40,569 unique sites of HIV integration. Computational prediction of nucleosome positions in target DNA indicated that integration sites are periodically distributed on the nucleosome surface, consistent with favored integration into outward-facing DNA major grooves in chromatin. Analysis of integration site positions in the densely annotated ENCODE regions revealed a wealth of new associations between integration frequency and genomic features. Integration was particularly favored near transcription-associated histone modifications, including H3 acetylation, H4 acetylation, and H3 K4 methylation, but was disfavored in regions rich in transcription-inhibiting modifications, which include H3 K27 trimethylation and DNA CpG methylation. Statistical modeling indicated that effects of histone modification on HIV integration were partially independent of other genomic features influencing integration. The pyrosequencing and bioinformatic methods described here should be useful for investigating many aspects of retroviral DNA integration.