ROLE OF ETS1 IN LYMPHOID CELLS

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ETS1 is a transcription factor capable of binding to purine rich core motif (-GGAA-) present in the promoter/enhancers of many cellular genes. The ETS1 gene expression is induced during late stages of thymocyte differentiation. ETS1 gene is expressed at high levels in resting T- cells and at very low levels after T-cell activation, suggesting that the ETS1 may regulate genes induced during T-cell activation. To elucidate the molecular mechanisms involved in ETS1 function in T-cells, sense, antisense and variant forms of ETS1 (ETS1 lacking DNA binding domain, ETS1 DNA binding domain and their mutant forms) are ectopically expressed in Jurkat T-cells. Jurkat T-cell transfectants with exogenous antisense ETS1 block the formation of ETS1 protein and produces higher levels of interleukin-2 compared to sense ETS1 and antisense ETS2 transfectants. The production of IL-2 in antisense ETS1 transfectants is inversely related to the levels of reinduced ETS1. The IL-2 promoter linked to a CAT reporter gene has high activity in antisense transfectants, suggesting increased IL-2 production appears to be due to transcriptional induction. Expression of sense ETS1 and ETS2 DNA binding domain protein reduces the formation of interleukin-2, further supporting our notion that the ETS1 negatively regulates IL-2 gene expression. Experiments are in progress to investigate the role of ETS1 in the transcriptional and post-transcriptional induction of lymphokine genes and in other ets target genes.