THE ETS TRANSCRIPTION FACTORS INTERACT WITH EACH OTHER AND WITH THE C-FOS C-JUN COMPLEX VIA DISTINCT PROTEIN DOMAINS IN A DNA-DEPENDENT ANDDNA-INDEPENDENT MANNER/

The transcription factors Fos,Jun, and Ets regulate the expression of human stromelysin-1 and collagenase-1 genes, Recently, we found that E RG, an Ets family member, activates collagenase-1 gene but not stromel y-sin-1 by physically interacting with c-Fos/c-Jun, Interestingly, ERG binds to stromelysin-1 promoter and represses its activation by ETS2. Here, to investigate the molecular mechanism of this regulation, we h ave used an in vitro protein-protein interaction assay and studied the transcription factor interactions of ETS2. We found that ETS2 could w eakly associate with in vitro synthesized ETS1, c-Fos, and c-Jun and s trongly with c-Fos/c-Jun complex and ERG via several distinct ETS2: do mains including the C-terminal region that contains the DNA-binding do main, Strikingly, these interactions were stabilized in vitro by DNA a s they were inhibited by ethidium bromide, Both the N-terminal region, comprising the transactivation domain, and the C-terminal region of E TS2 associated with ERG and, interestingly, the interaction of ERG thr ough the transactivation domain of ETS2 was DNA-independent, The DNA-d ependent interaction of ETS2 with c-Fos/c-Jun was enhanced by specific DNA fragments requiring two Ets-binding-sites of the stromelysin-1 pr omoter, Using the two hybrid system, we also demonstrated that ETS2 in teracts with c-Jun or ERG in vivo.