A novel ets-related transcription factor, ERT/ESX/ESE-1, regulates expression of the transforming growth factor-beta type II receptor.

Abstract

A 2.5-kilobase cDNA clone that encodes a 371-amino acid novel transcription factor was isolated from a human placenta cDNA library using a yeast one-hybrid system. The novel ets-related transcription factor (ERT) showed a homology with the ETS DNA-binding domain. Using constructs of the transforming growth factor-beta (TGF-beta) type II receptor (RII) promoter linked to the luciferase gene, we have demonstrated that ERT activates transcription of the TGF-beta RII gene through the 5'-TTTCCTGTTTCC-3' response element spanning nucleotides +13 to +24 and multiple additional ETS binding sites between -1816 and -82 of the TGF-beta RII promoter. A specific interaction between ERT and the ETS binding sites was also demonstrated using an electrophoretic mobility shift assay. Deletion mapping of ERT protein suggests that the transactivation domain resides in the amino terminus while the DNA-binding domain is localized to the carboxyl-terminal region. Our results suggest that ERT might be a major transcription factor involved in the transcriptional regulation of the TGF-beta RII gene.