期刊论文详细信息
PLoS Pathogens
LANA Binds to Multiple Active Viral and Cellular Promoters and Associates with the H3K4Methyltransferase hSET1 Complex
Yajie Yang1  Jianhong Hu1  Peter C. Turner1  Vaibhav Jain1  Lauren M. McIntyre1  Rolf Renne2 
[1] Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America;UF Genetics Institute, University of Florida, Gainesville, Florida, United States of America
关键词: Sequence motif analysis;    Cell binding;    Transcription factors;    Chromatin;    Sequence alignment;    DNA transcription;    Human genomics;    Histones;   
DOI  :  10.1371/journal.ppat.1004240
学科分类:生物科学(综合)
来源: Public Library of Science
PDF
【 摘 要 】

Kaposi's sarcoma-associated herpesvirus (KSHV) is a γ-herpesvirus associated with KS and two lymphoproliferative diseases. Recent studies characterized epigenetic modification of KSHV episomes during latency and determined that latency-associated genes are associated with H3K4me3 while most lytic genes are associated with the silencing mark H3K27me3. Since the latency-associated nuclear antigen (LANA) (i) is expressed very early after de novo infection, (ii) interacts with transcriptional regulators and chromatin remodelers, and (iii) regulates the LANA and RTA promoters, we hypothesized that LANA may contribute to the establishment of latency through epigenetic control. We performed a detailed ChIP-seq analysis in cells of lymphoid and endothelial origin and compared H3K4me3, H3K27me3, polII, and LANA occupancy. On viral episomes LANA binding was detected at numerous lytic and latent promoters, which were transactivated by LANA using reporter assays. LANA binding was highly enriched at H3K4me3 peaks and this co-occupancy was also detected on many host gene promoters. Bioinformatic analysis of enriched LANA binding sites in combination with biochemical binding studies revealed three distinct binding patterns. A small subset of LANA binding sites showed sequence homology to the characterized LBS1/2 sequence in the viral terminal repeat. A large number of sites contained a novel LANA binding motif (TCCAT)3 which was confirmed by gel shift analysis. Third, some viral and cellular promoters did not contain LANA binding sites and are likely enriched through protein/protein interaction. LANA was associated with H3K4me3 marks and in PEL cells 86% of all LANA bound promoters were transcriptionally active, leading to the hypothesis that LANA interacts with the machinery that methylates H3K4. Co-immunoprecipitation demonstrated LANA association with endogenous hSET1 complexes in both lymphoid and endothelial cells suggesting that LANA may contribute to the epigenetic profile of KSHV episomes.

【 授权许可】

CC BY   

【 预 览 】
附件列表
Files Size Format View
RO201902016713758ZK.pdf 1901KB PDF download
  文献评价指标  
  下载次数:12次 浏览次数:22次