DNA methylation at hepatitis B viral integrants is associated with methylation at flanking human genomic sequences.
DNA methylation at hepatitis B viral integrants is associated with methylation at flanking human genomic sequences.
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DOI：
10.1101/gr.175240.114
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发表时间：
2015-03
期刊：
影响因子：
7
通讯作者：
Itoh F
中科院分区：
文献类型：
--
作者：
Watanabe Y;Yamamoto H;Oikawa R;Toyota M;Yamamoto M;Kokudo N;Tanaka S;Arii S;Yotsuyanagi H;Koike K;Itoh F
DNA病毒整合到人类基因组中在各种类型的肿瘤中起重要作用，包括与B型肝炎病毒（HBV）相关的肝细胞癌。然而，HBV整合对人类或HBV表观基因组的分子细节和临床影响尚不清楚。在这里，我们发现整合的HBV DNA的甲基化与侧翼人类基因组的甲基化状态有关。我们开发了下一代基于测序的方法，用于整合病毒基因组的结构甲基化分析（表示为G-NaVI）。该方法是一种新的方法，其能够使用基于HBV基因组序列的独特诱饵富集用于测序的病毒片段。我们在PLC/PRF/5细胞系的基因组中检测到整合的HBV序列，并在整合的HBV基因组中发现不同水平的甲基化。等位基因特异性甲基化分析表明，HBV基因组往往成为显着甲基化时，整合到高度甲基化的主机网站。然而，在整合到未甲基化的人类基因组区域（如启动子）后，HBV DNA保持未甲基化，并可能最终在肿瘤发生中发挥重要作用。宿主和病毒基因组DNA甲基化的动态变化可能在功能上影响HBV的生物学行为。这些发现可能会影响公共卫生，因为全世界有数百万人是HBV携带者。我们也相信我们的检测将是一个强大的工具，以增加我们对各种类型的DNA病毒相关的肿瘤发生的理解。
Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)–related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either human or HBV epigenomes are unknown. Here, we show that methylation of the integrated HBV DNA is related to the methylation status of the flanking human genome. We developed a next-generation sequencing-based method for structural methylation analysis of integrated viral genomes (denoted G-NaVI). This method is a novel approach that enables enrichment of viral fragments for sequencing using unique baits based on the sequence of the HBV genome. We detected integrated HBV sequences in the genome of the PLC/PRF/5 cell line and found variable levels of methylation within the integrated HBV genomes. Allele-specific methylation analysis revealed that the HBV genome often became significantly methylated when integrated into highly methylated host sites. After integration into unmethylated human genome regions such as promoters, however, the HBV DNA remains unmethylated and may eventually play an important role in tumorigenesis. The observed dynamic changes in DNA methylation of the host and viral genomes may functionally affect the biological behavior of HBV. These findings may impact public health given that millions of people worldwide are carriers of HBV. We also believe our assay will be a powerful tool to increase our understanding of the various types of DNA virus-associated tumorigenesis.
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影响因子：
3.5
作者：
Furey, TS;Haussler, D
通讯作者：
Haussler, D
DOI：
10.1073/pnas.84.4.1005
发表时间：
1987-02-01
影响因子：
11.1
作者：
SELLS, MA;CHEN, ML;ACS, G
通讯作者：
ACS, G
影响因子：
4.4
作者：
MINAMI, M;POUSSIN, K;PATERLINI, P
通讯作者：
PATERLINI, P
影响因子：
50.3
作者：
Lau, Chi-Chiu;Sun, Tingting;Wong, Nathalie
通讯作者：
Wong, Nathalie
影响因子：
7
作者：
Jiang, Zhaoshi;Jhunjhunwala, Suchit;Zhang, Zemin
通讯作者：
Zhang, Zemin