Role of ETS1 in IL-2 gene expression.
The ETS1 gene encodes a sequence-specific transcription factor binding to purine-rich DNA sequences (-GGAA-) present in the transcriptional regulatory regions of many cellular and viral promoters/enhancers, including many lymphokine genes. The ETS1 gene is expressed at high levels in resting T cells and at very low levels after T cell activation, suggesting it may suppress the expression of genes induced during T cell activation. To find out if ETS1 regulates expression of the IL-2 gene, we have ectopically expressed antisense (AS) ETS1 in Jurkat T cells to block the formation of ETS1 proteins. AS ETS1 transfectants produce higher levels of IL-2 compared with sense ETS1 transfectants. Expression of ETS1 DNA binding domain in Jurkat T cells also decreased the production of IL-2. In AS ETS1 transfectants, IL-2 formation was completely inhibited by cyclosporin A and FK590. The IL-2 promoter linked to a chloramphenicol acetyl transferase reporter gene has high activity in AS ETS1 transfectants, indicating that increased IL-2 production seems to be a result of transcriptional induction. Taken together, these results suggest the possibility that ETS1 may act as a negative regulator of IL-2 gene transcription and provide a rational approach toward engineering the endogenous expression of IL-2 in T cells.
Romano-Spica
V
V
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, MD 21702.
Georgiou
P
P
Suzuki
H
H
Papas
T S
TS
Bhat
N K
NK
D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics*; D015759:Ionomycin / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D050783:Proto-Oncogene Proteins c-ets; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection / Q000235:genetics
C494041:ETS1 protein, human; D007376:Interleukin-2; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D015759:Ionomycin; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate