Early Growth Response gene 1 (Egr-1) regulates HSV-1 ICP4 and ICP22 gene expression  

作　　者：Gautam R Bedadala Rajeswara C Pinnoji Shao-Chung V Hsia 

机构地区：[1]Department of Basic Pharmaceutical Sciences,College of Pharmacy, The University of Louisiana at Monroe, 700 University Avenue,Monroe,LA 71209, USA

出　　处：《Cell Research》2007年第6期546-555,共10页细胞研究（英文版）

摘　　要：The molecular mechanisms mediating herpes simplex virus type 1 （HSV- 1） gene silencing during latent infection are not clear. Five copies of early growth response gene 1 （Egr-1） binding elements were identified in the intron of HSVol ICP22 （infected cell protein No. 22） gene, leading to the hypothesis that Egro 1 binds to the viral genome and regulates the viral gene expression. Transient co-transfection assays indicated that Egr-1 negatively regulated the transcription of both full-length and intron-removed ICP22 promoters. The same assays also revealed that Egr-1 repressed ICP4 （infected cell protein No. 4） promoter activity in a dose-dependent manner but showed less inhibition when the intron was removed. Histone deacetylation was not involved in this regulation since histone deacetylase inhibitor trichostatin A did not exhibit any effect on Egr-l-mediated repression. Chromatin immunoprecipitation assays showed that Egr-1 reduced the binding of Spl to the promoters and that the co-repressor Nab2 （NGFI-A/EGRl-binding protein） was recruited to the proximity of ICP4 in the presence of Egr-1. These results suggested that the multi functional transcription factor Egr-1 can repress HSV-1 immediate-early gene expression through the recruitment ofco-repressor Nab2 and reduction of Sp 1 occupancy, and thus may play a critical role in HSV-1 gene silencing during latency.

关 键 词：HSV-1 LATENCY EGR-1 Sp 1 Nab2 transcription regulation 

分 类 号：R373[医药卫生—病原生物学]