Delineation of an enhancerlike positive regulatory element in the interleukin-2 receptor alpha-chain gene.
We have delineated a positive regulatory element in the interleukin-2 receptor alpha-chain gene (IL-2R alpha) between positions -299 and -243 that can potently activate a heterologous (herpesvirus thymidine kinase [tk]) promoter in phorbol myristate acetate (PMA)-induced Jurkat T cells and is functional when cloned in either orientation. This enhancerlike element contains a site (-268/-257) that can bind NF-kappa B; however, unlike the immunoglobulin kappa gene kappa B enhancer element, the IL-2R alpha kappa B-like site alone can only weakly activate a heterologous promoter. Adjacent 5' and 3' sequences also weakly activate the tk-CAT vector, but constructs combining the IL-2R alpha kappa B-like site plus adjacent 5' and 3' sequences potently activate gene expression. This combination of regions is essential for potent PMA-induced transcription from the tk promoter. Experiments using constructs in which IL-2R alpha upstream sequences are sequentially deleted suggested that there is a region 5' of position -299 which can suppress IL-2R alpha promoter and/or enhancer activity. Thus, it is possible that both positive and negative elements may be important in the regulation of IL-2R alpha gene transcription.
Lin
B B
BB
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Cross
S L
SL
Halden
N F
NF
Roman
D G
DG
Toledano
M B
MB
Leonard
W J
WJ
D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002872:Chromosome Deletion; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D005796:Genes; D006801:Humans; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013937:Thymidine Kinase / Q000235:genetics
D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D015375:Receptors, Interleukin-2; D015500:Chloramphenicol O-Acetyltransferase; D013937:Thymidine Kinase; D013755:Tetradecanoylphorbol Acetate