The early growth response protein (EGR-1) regulates interleukin-2 transcription by synergistic interaction with the nuclear factor of activated T cells.
The early growth response-1 gene (EGR-1) is induced by a wide range of stimuli in diverse cell types; however, EGR-1-regulated genes display a highly restricted pattern of expression. Recently, an overlapping Sp1.EGR-1 binding site has been identified within the interleukin-2 (IL-2) gene promoter directly upstream of the binding site for the nuclear factor of activated T cells (NFAT). We used transfection assays to study how the abundantly and constitutively expressed Sp1 protein and the immediate early EGR-1 zinc finger protein regulate IL-2 gene expression. Here, we identify EGR-1 as an important activator of the IL-2 gene. In Jurkat T cells, EGR-1 but not Sp1 acts as a potent coactivator for IL-2 transcription, and in combination with NFATc, EGR-1 increases transcription of an IL-2 reporter construct 200-fold. Electrophoretic mobility shift assays reveal that recombinant EGR-1 and NFATc bind independently to their target sites within the IL-2 promoter, and the presence of both sites on the same DNA molecule is required for EGR-1.NFATc.DNA complex formation. The transcriptional synergy observed here for EGR-1 and NFATc explains how the abundant nuclear factor EGR-1 contributes to the expression of restrictively expressed genes.
Decker
E L
EL
Research Group of Biomolecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, D-20359 Hamburg, Germany.
Skerka
C
C
Zipfel
P F
PF
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins; D007376:Interleukin-2 / Q000235:genetics*; D019169:Jurkat Cells; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors