T-CELL FUNCTIONAL REGIONS OF THE HUMAN IL-3 PROXIMAL PROMOTER

The human interleukin-3 (IL-3) gene is expressed almost exclusively in activated T cells. Its expression is regulated at both the transcript ional and post-transcriptional level. We have previously shown that tr eatment of Jurkat T cells with phytohemaglutinin (PHA) and the phorbol ester, PMA, activated transcription initiation from the IL-3 gene. To define the regions of the gene required for transcription activation, we generated a series of reporter constructs containing different reg ions of the IL-3 gene 5' and 3' flanking sequences. Both positive and negative regulatory elements were identified in the proximal 5' flanki ng region of the IL-3 gene. The promoter region between -173 and -60 c ontained the strongest activating elements. The transcription factor A P-1 could bind to this positive activator region of the promoter. We a lso examined the function of the IL-3 CK-1/CK-2 elements that are pres ent in many cytokine genes and found that they acted as a repressor of basal level expression when cloned upstream of a heterologous promote r but were also inducible by PMA/PHA. (C) 1994 Wiley-Liss, Inc.