title: Early growth response gene 1 (Egr-1) regulates HSV-1 ICP4 and ICP22 gene expression.
abstract: 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.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209, USA.
authors.forename: Gautam R
authors.initials: GR
authors.lastname: Bedadala
authors.forename: Rajeswara C
authors.initials: RC
authors.lastname: Pinnoji
authors.forename: Shao-Chung V
authors.initials: SC
authors.lastname: Hsia
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000502:physiology*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D020868:Gene Silencing; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics*; D007438:Introns / Q000235:genetics; D014775:Virus Activation / Q000235:genetics; D017735:Virus Latency / Q000235:genetics
chemical_list: D051766:Early Growth Response Protein 1; C057294:ICP22 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; C048925:herpes simplex virus, type 1 protein ICP4