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

doi:10.1128/JVI.01392-15

	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
	Dong, YH; Zhang, H; Hu, H; Sun, R; Bai, L; Gao, ZQ; Liang, DG; Dong, JZ; Hu, HD; Dong YH(董宇辉)
刊名	JOURNAL OF VIROLOGY
	2016
卷号	90 期号:3 页码:1158-1168
ISSN号	0022-538X
DOI	10.1128/JVI.01392-15
文献子类	Article
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.
电子版国际标准刊号	1098-5514
语种	英语
WOS记录号	WOS:000369150800001
内容类型	期刊论文
源URL	[http://ir.ihep.ac.cn/handle/311005/287064]
专题	中国科学院高能物理研究所
推荐引用方式 GB/T 7714	Dong, YH,Zhang, H,Hu, H,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	Dong, YH.,Zhang, H.,Hu, H.,Sun, R.,Bai, L.,...&Lan, K.(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	Dong, YH,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.