Modulation of early growth response (EGR) transcription factor-dependent gene expression by using recombinant adenovirus

Early growth response (EGR) transcription factors link initial cytoplasmic events to long-term alterations of cellular gene expression and are induced by various stimuli. To test their roles in cell physiology, we constructed adenoviral recombinants encoding NGFI-A binding protein 2 (NAB2, a repress or of EGR1, EGR2, and EGR3), EGR1, NAB-insensitive EGR1(I293F) (EGR1*), EGR 2, and the NAB-binding, repressive domain 1 (R1) of EGR1. These viruses reg ulated EGR-dependent expression of GFP and luciferase reporter genes in het erologous expression assays. Infection of a myoblast cell line with EGR1 an d EGR1* adenovirus induced the endogenous gene for platelet-derived growth factor A chain (PDGF-A). In addition, in neuroblastoma cells, the two novel EGR1 target genes EGR3 and NAB2 were identified by using adenoviral transf er of EGR1 and EGR1*. Our results demonstrate that recombinant adenovirus i s useful to regulate heterologous and endogenous EGR target gene expression , and suggest that EGR transcription factors can autoregulate themselves. ( C) 2000 Elsevier Science B.V. All rights reserved.