NEW HUMAN ERG ISOFORMS GENERATED BY ALTERNATIVE SPLICING ARE TRANSCRIPTIONAL ACTIVATORS

The erg gene is a member of the ets gene family. ETS proteins have bee n shown to bind specifically the (GGAA/T) motif and to transactivate v ia this consensus sequence. The human erg products exhibit almost-equa l-to 70% homology with ETS proteins in their DNA-binding domain. We ha ve isolated three erg cDNAs from a human fetal liver library. Two of t hem are different from the previously described erg-1 and erg-2 cDNAs (Rao et al., Science, 1987, 237, 635-639), in the middle of their codi ng sequence and in their 5' part where a novel initiation codon is int roduced. These isoforms are generated by alternative RNA splicing from a single gene that leads to the inclusion or exclusion of different e xon sequences. The three cDNAs expressed by an in vitro transcription- translation system direct the synthesis of proteins of almost-equal-to 38, 49 and 55 kDa. These in vitro erg products were tested for their DNA-binding activity by gel mobility-shift assays with different probe s containing the ETS-specific binding site. The results indicated that all these erg isoforms are able to bind the ETS binding site in a spe cific manner. Our data using transient transfection assays indicate th at erg protein isoforms function as transcriptional activators.