ROLE OF ETS1 IN LYMPHOID CELLS

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The ets family of genes encodes transcription factors, binds to purine- rich motifs (A/CGGAAGT/C), and regulates promoter/enhancer activities of cellular and viral genes. Members of the ets family include: ETS1, ETS2, ERG, ELK, ERGB/FLI, PU.1/SpiI, ELF1, GABPalpha, PEA3, ER81, and ER71 genes. To understand the function of the ets family of genes during hematopoietic differentiation, well-characterized cell lines representing erythroid, myeloid, and lymphoid lineages have been used to study ets expression by RNA blot analyses. The expression of PEA3 and ERG was higher in the myeloid precursor cell lineage than in functionally-mature myeloid cells. The GABPalpha, ETS2 mRNAs are expressed in most of the cell lines studied. However, ETS1 expression was much higher in lymphoid cells than in cells of myeloid or erythroid origin. ERGB, GABPalpha, GABPbeta and ETS2 was also expressed in thymocytes and splenic B- and T- cells. During T-cell activation by mitogens, both ETS1 and ERGB expression was reduced. Stimulation of promyelocytic cell line HL60 by phorbol esters, GABPalpha and beta mRNAs is induced during an early phase of differentiation. Therefore, it appears that ets gene products may play a role in cell growth, differentiation, and functional maturation of hematopoietic cells. To elucidate the role of the ets family of genes in T-cells, eukaryotic expression vectors containing the DNA-binding domain and variant forms of ETS1 were transfected into Jurkat T-cells by electro- poration, and independent clones were selected in G418. Characterization of these clones for expression of exogenous ets gene products, and their effect on target genes, is in progress. In particular, FACS and RNA blot analysis reflecting the expression pattern of surface antigen and growth properties of the transfected cells (growth rate, tumorigenesis), the production of lymphokines (RNA and ELISA), and the modulation of activities of specific candidate genes targeted by the ets family of genes (RNA blots, CAT assays, differential display), are being performed.