ETS1 TRANSACTIVATES THE HUMAN GM-CSF PROMOTER IN JURKAT T-CELLS STIMULATED WITH PMA AND IONOMYCIN

Activation of T helper cells results in coordinate expression of a num ber of cytokines involved in differentiation, proliferation and activa tion of the haematopoietic system. Granulocyte-macrophage colony-stimu lating factor (GM-CSF) is one such cytokine whose increased expression results partly from increases in transcription. Cis-acting elements w ith NF kappa B, AP-1 and ETS-like motifs have been identified in the p romoter region of the GM-CSF gene, which are important for transcripti onal activity following PMA and ionomycin stimulation. A number of the ETS family of transcription factors are expressed in T cells, includi ng ETS1 and ELF1. Here we describe the ability of these factors to int eract with a site (GM5), located within the CLE0 element, -47 to -40 u pstream of the GM-CSF transcription initiation site. Exogenous ETS1, b ut not ELF1, can transactivate GM-CSF, through the GM5 site, in a PMA/ ionomycin dependent manner. Other unidentified ETS-like factors presen t in Jurkat cells are also capable of binding GM5. Mutation of the cor e ETS binding site from -GGAA- to -GGAT- prevents the binding of ETS-l ike factors with the exception of ETS1. The GM-CSF promoter, modified in this way to be ETS1 specific, is fully responsive to PMA/ionomycin induction, in addition to ETS1 transactivation in the presence of PMA and ionomycin. Together these data suggest that ETS1 may be involved i n mediating the increased GM-CSF production associated with T cell act ivation.