Volume 17, No 6, Jun 2007

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 17 Issue 6, June 2007: 546-555

ORIGINAL ARTICLES

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

Gautam R Bedadala, Rajeswara C Pinnoji and Shao-Chung V Hsia

Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209, USA Correspondence: Shao-Chung V Hsia(hsia@ulm.edu)

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 HSV-1 ICP22 (infected cell protein No. 22) gene, leading to the hypothesis that Egr-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-1-mediated repression. Chromatin immunoprecipitation assays showed that Egr-1 reduced the binding of Sp1 to the promoters and that the co-repressor Nab2 (NGFI-A/EGR1-binding protein) was recruited to the proximity of ICP4 in the presence of Egr-1. These results suggested that the multifunctional transcription factor Egr-1 can repress HSV-1 immediate-early gene expression through the recruitment of co-repressor Nab2 and reduction of Sp1 occupancy, and thus may play a critical role in HSV-1 gene silencing during latency.

Cell Research (2007) 17:546-555. doi: 10.1038/cr.2007.44; published online 15 May 2007

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