PEA3, Oct 1 and Oct 2 positively regulate the human ETS1 promoter

Abstract

The promoter of the human ETS1 gene contains binding site motifs for transcription factors Sp1, Ap1, Ap2, ETS, PEA3 and Oct. It has been shown previously that Ap1, Ap2, and ETS are positive regulators for the transcription of the ETS1 gene and that the ETS1 gene is autoregulated. In addition, two regions on the ETS1 promoter that contain negative regulatory sequences have also been identified. In this study, GST/PEA3 and GST/ets1 fusion proteins were used in gel mobility assays to analyse the interaction between these transcription factors with the binding motifs of PEA3 and ETS in the ETS1 promoter. Promoter constructs in which the binding site motifs are mutated were used to examine the effect of mutation on the activities of transcription factors PEA3, ets1 and Oct. Reporter plasmids containing different deletion mutants of the ETS1 promoter were used to examine the effect of different transcription factors (PEA3, Oct 1 and Oct 2) upon the expression of the ETS1 gene. The results of these studies indicate that PEA3 is a strong positive regulator of the ETS1 promoter and that other transcription factors increase the activity of the ETS1 promoter in an additive rather than synergistic fashion.