Positive and negative factors regulate the transcription of the ETS2 gene via an oncogene-responsive-like unit within the ETS2 promoter region.

The DNA-protein interactions in the ETS2 promoter have been studied. Three distinct sequence motifs have been identified, each of which interacts with at least two distinctive protein complexes. The GC motif, possessing mirror symmetry, interacts with two ubiquitously identifiable complexes (S and S2); the PEA3 motif interacts with a ubiquitous (H1) and a tissue-specific (H3) complex; the H2 (an AP1-like) motif interacts also with a ubiquitous (H2a) and a tissue-specific (H2b) complex. Mutational analysis and correlation of the presence of defined complexes with the ETS2 mRNA levels indicate that the S, S2, H1, and H2b complexes have positive effects on ETS2 transcription, whereas the H3 and H2a have negative effects. The organization of the PEA3 with the AP1-like motif in the ETS2 promoter resembles the oncogene-responsive unit previously identified in the polyoma virus enhancer region. Our data suggest that cooperation between these two motifs is vital for ETS2 promoter function.