Genome-wide mapping of the binding sites and structural analysis of kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 2 reveal that it is a dna-binding transcription factor
文献类型:期刊论文
作者 | Hu, Haidai1; Dong, Jiazhen1; Liang, Deguang1; Gao, Zengqiang2; Bai, Lei1; Sun, Rui1; Hu, Hao1; Zhang, Heng2; Dong, Yuhui2; Lan, Ke1 |
刊名 | Journal of virology
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出版日期 | 2016-02-01 |
卷号 | 90期号:3页码:1158-1168 |
ISSN号 | 0022-538X |
DOI | 10.1128/jvi.01392-15 |
通讯作者 | Dong, yuhui(dongyh@ihep.ac.cn) ; Lan, ke(lanke@ips.ac.cn) |
英文摘要 | The oncogenic herpesvirus kaposi's sarcoma-associated herpesvirus (kshv) is known to encode four viral interferon regulatory factors (virf1 to -4) to subvert the host antiviral immune response, but their detailed dna-binding profiles as transcription factors in the host remain uncharacterized. here, we first performed genome-wide virf2-binding site mapping in the human genome using chromatin immunoprecipitation coupled with high-throughput sequencing (chip-seq). virf2 was capable of binding to the promoter regions of 100 putative target genes. importantly, we confirmed that virf2 can specifically interact with the promoters of the genes encoding pik3c3, hmgcr, and hmgcl, which are associated with autophagosome formation or tumor progression and metastasis, and regulate their transcription in vivo. the crystal structure of the virf2 dna-binding domain (dbd) (referred to here as virf2(dbd)) showed variable loop conformations and positive-charge distributions different from those of virf1 and cellular irfs that are associated with dna-binding specificities. structure-based mutagenesis revealed that arg82 and arg85 are required for the in vitro dna-binding activity of virf2dbd and can abolish the transcription regulation function of virf2 on the promoter reporter activity of pik3c3, hmgcr, and hmgcl. collectively, our study provided unique insights into the dna-binding potency of virf2 and suggested that virf2 could act as a transcription factor of its target genes in the host antiviral immune response. |
WOS关键词 | PROTEIN ; IDENTIFICATION ; MODEL ; GENE ; HUMAN-HERPESVIRUS-8 ; REPLICATION ; INHIBITION ; ANNOTATION ; METABOLISM ; EXPRESSION |
WOS研究方向 | Virology |
WOS类目 | Virology |
语种 | 英语 |
WOS记录号 | WOS:000369150800001 |
出版者 | AMER SOC MICROBIOLOGY |
URI标识 | http://www.irgrid.ac.cn/handle/1471x/2176567 |
专题 | 高能物理研究所 |
通讯作者 | Dong, Yuhui; Lan, Ke |
作者单位 | 1.Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China 2.Chinese Acad Sci, Inst High Energy Phys, Beijing Synchrotron Radiat Facil, Beijing, Peoples R China |
推荐引用方式 GB/T 7714 | Hu, Haidai,Dong, Jiazhen,Liang, Deguang,et al. Genome-wide mapping of the binding sites and structural analysis of kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 2 reveal that it is a dna-binding transcription factor[J]. Journal of virology,2016,90(3):1158-1168. |
APA | Hu, Haidai.,Dong, Jiazhen.,Liang, Deguang.,Gao, Zengqiang.,Bai, Lei.,...&Lan, Ke.(2016).Genome-wide mapping of the binding sites and structural analysis of kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 2 reveal that it is a dna-binding transcription factor.Journal of virology,90(3),1158-1168. |
MLA | Hu, Haidai,et al."Genome-wide mapping of the binding sites and structural analysis of kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 2 reveal that it is a dna-binding transcription factor".Journal of virology 90.3(2016):1158-1168. |
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来源:高能物理研究所
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