The promoter of the human interleukin-2 gene contains two octamer-binding sites and is partially activated by the expression of Oct-2.
The gene encoding interleukin-2 (IL-2) contains a sequence 52 to 326 nucleotides upstream of its transcriptional initiation site that promotes transcription in T cells that have been activated by costimulation with tetradecanoyl phorbol myristyl acetate (TPA) and phytohemagglutinin (PHA). We found that the ubiquitous transcription factor, Oct-1, bound to two previously identified motifs within the human IL-2 enhancer, centered at nucleotides -74 and -251. Each site in the IL-2 enhancer that bound Oct-1 in vitro was also required to achieve a maximal transcriptional response to TPA plus PHA in vivo. Point mutations within either the proximal or distal octamer sequences reduced the response of the enhancer to activation by 54 and 34%, respectively. Because the murine T-cell line EL4 constitutively expresses Oct-2 and requires only TPA to induce transcription of the IL-2 gene, the effect of Oct-2 expression on activation of the IL-2 promoter in Jurkat T cells was determined. Expression of Oct-2 potentiated transcription 13-fold in response to TPA plus PHA and permitted the enhancer to respond to the single stimulus of TPA. Therefore, both the signal requirements and the magnitude of the transcription response of the IL-2 promoter can be modulated by Oct-2.
Whitehead Institute for Biomedical Research, Cambridge Center, Massachusetts 02142.
M P
MP
Kamps
L
L
Corcoran
J H
JH
LeBowitz
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D
Baltimore
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000235:genetics*; D008745:Methylation; D008969:Molecular Sequence Data; D050813:Octamer Transcription Factor-2; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D050813:Octamer Transcription Factor-2; C058435:POU2F2 protein, human; D014157:Transcription Factors