ETS FAMILY PROTEINS ACTIVATE TRANSCRIPTION FROM HIV-1 LONG TERMINAL REPEAT

ets is a multigene family and its members share a common ETS DNA-bindi ng domain. ETS proteins activate transcription via binding to a purine -rich GGAA core sequence located in promoters/enhancers of various gen es, including several that are transcriptionally active in T cells. Th e ETS1, ETS2, and ERBG/Hu-FLI-1 gene expression pattern also suggests a role for these genes in cells of hematopoietic lineage. The HIV-1 LT R core enhancer contains two 10-base pair direct repeat sequences (lef t and right) that are required for regulation of HIV-1 mRNA expression by host transcription factors, including NFkappaB. Two ETS-binding si tes are present in the core enhancer of all the HIV-1 isolates reporte d so far. In our studies, we utilized HIV-1 HXB2 and HIV-1 Z2Z6 core e nhancers because the Z2Z6 strain has a single point mutation flanking the right ETS-binding site. We demonstrate that the ETS1, ETS2, and ER GB/Hu-FLI-1 proteins can trans-activate transcription from both the HX B2 and Z2Z6 core enhancer when linked to a reporter (cat) gene. In add ition, we show that the DNA binding and trans-activation with the Z2Z6 core enhancer is at least 40-fold higher than that observed with the HXB2 core enhancer. Further, we provide evidence that the marked incre ase in binding and trans-activation with Z2Z6 core enhancer sequences is due to the substitution of a flanking T residue in HXB2 TGGAA) by a C residue in Z2Z6 (CGGAA) isolate, thus generating an optimal ETS-bin ding core (CGGAA) sequence.