Functional analysis of the human interleukin 2 receptor γ chain gene promoter

The third component of the interleukin (IL) 2 receptor, γ chain, is essential not only for IL-2- but also for IL-4-, IL-7-, IL-9-, and IL-15- induced proliferation of lymphocytes. To elucidate the mechanisms by which the γ chain is expressed, we have analyzed the promoter region of the γ chain gene. The 633-base pair fragment upstream of the initiation codon showed the promoter activity in human hematopoietic cell lines, Jurkat and THP-1, when linked to the luciferase gene. With a series of 5'-deletion mutants, the basal promoter activity was found in a fragment from nucleotide 80 to 58 upstream from the RNA start site, including an Ets binding sequence. Treatment of cells with either 12-O-tetradecanoylphorbol-13-acetate or phytohemagglutinin but not forskolin induced transcription from the γ chain gene promoter. A viral trans-acting transcriptional activator, Tax, of human T-cell leukemia virus type I elevated expression of the γ chain gene. In contrast, IL-2 decreased transcription from the IL-2 receptor γ chain promoter. These results suggest that expression of the γ chain is regulated at the transcription level by extracellular stimuli and may be implicated in immune response.