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 repressor of EGR1, EGR2, and EGR3), EGR1, NAB-insensitive EGR1(I293F) (EGR1*), EGR2, and the NAB-binding, repressive domain 1 (R1) of EGR1. These viruses regulated EGR-dependent expression of GFP and luciferase reporter genes in heterologous expression assays. Infection of a myoblast cell line with EGR1 and 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 transfer of EGR1 and EGR1*. Our results demonstrate that recombinant adenovirus is useful to regulate heterologous and endogenous EGR target gene expression, and suggest that EGR transcription factors can autoregulate themselves.
Ehrengruber
M U
MU
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland. ehrengru@hifo.unizh.ch
Muhlebach
S G
SG
Söhrman
S
S
Leutenegger
C M
CM
Lester
H A
HA
Davidson
N
N
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D051776:Early Growth Response Protein 3; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000502:physiology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D008164:Luminescent Proteins; C491000:NAB2 protein, human; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C075278:platelet-derived growth factor A; D051776:Early Growth Response Protein 3; D049452:Green Fluorescent Proteins