ELF-1 REGULATES BASAL EXPRESSION FROM THE T-CELL ANTIGEN RECEPTOR ZETA-CHAIN GENE PROMOTER

In mature T cells, limited synthesis of the TCR-zeta subunit is primar ily responsible for regulating surface expression of TCRs, Transcripti on of zeta is directed by a complex promoter that includes two potenti al binding sites for the Ets family of transcription factors at -52 (2 EBS1) and -135 (zEBS2), Mutation of these two sites results in a marke d reduction of transcription from this promoter, Using electrophoretic mobility shift analysis, Elf-1 was demonstrated to be the Ets family member that binds to these sites, One site, zEBS1, matches the optimal Elf-1 consensus sequence in eight of nine bases? making it the best m atch of any known mammalian Elf-1 binding site, A role for Elf-1 in TC R-zeta trans-activation was confirmed by ectopic expression of Elf-1 i n COS-7 cells, This resulted in an increase in TCR-zeta promoter activ ity that mapped to 2EBS1 and zEBS2, Additional support for the involve ment of Elf-1 in TCR-zeta trans-activation derives from the finding th at a GAL4-Elf-1 fusion protein trans-activated TCR-zeta promoter const ructs that had been modified to contain GAL4 DNA binding sites, These results demonstrate that Elf-1 plays an essential role in the trans-ac tivation of a constitutively expressed T cell-specific gene, and that trans-activation occurs in the context of the native promoter in both lymphoid and nonlymphoid cells. Taken together with the existing liter ature, these data also suggest that the requirement for inducible fact ors in Elf-1-mediated trans-activation may decrease as the affinity an d number of Elf-1 sites increase.