ERG PROTEINS, TRANSCRIPTION FACTORS OF THE ETS FAMILY, FORM HOMO, HETERODIMERS AND TERNARY COMPLEXES VIA 2 DISTINCT DOMAINS

The ets genes family encodes a group of proteins which function as tra nscription factors under physiological conditions. We report here that the Erg proteins, members of the Ets family, form homo and heterodime ric complexes in vitro. We demonstrate that the Ergp55 protein isoform forms dimers,vith itself and with the two other isoforms, Ergp49 and Ergp38. Using a set of Erg protein deletion mutants, we define two dis tinct domains independently involved in dimerization. The first one is located in the amino-terminal part of the protein containing the poin ted domain (PNT), conserved in a subset of Ets proteins. The second on e resides within the ETS domain, the DNA-binding domain. We also show that the Erg protein central region behaves as an inhibitory domain of dimerization and its removal enhances the Ergp55 transactivation prop erties. Furthermore, Ergp55 forms heterodimers with some other Ets pro teins. Among the latter, we show that Fli-1, Ets-2, Er81 and Pu-1 phys ically interact with Erg. Finally, rye show that the formation of the previously described ternary complex Ergp55/Fos/jun is mediated by ETS domain and Jun protein, while the ternary complex Ergp49/Fos/Jun is m ediated by Fos protein.