TBP-related factor 2 (TRF2), one of the TBP family proteins, is involved in various cellular functions through its transcription stimulation activity. We previously reported that TRF2 is involved in reduction of weel mRNA in genotoxin-treated chicken cells. In this study, we investigated the role of TRF2 in weel gene expression. It was found that weel mRNA was decreased in hydroxyurea-treated NIH3T3 cells. Mouse weel promoter activity was repressed by TRF2 in mouse and chicken cells. Chromatin immunoprecipitation and plasmid immunoprecipitation analyses revealed that TRF2 is recruited to the wee] promoter in accordance with the transcriptional repression. A mutant TRF2 that lacks THIA-binding capacity lost its repressive function. This mutant was less recruited to the weel promoter than was the wild-type one, and provided a decline in promoter-recruited TFIIA. Data in this study suggest that transcription repressive activity of TRF2 to weel promoter needs association with the promoter and THIA. (c) 2006 Elsevier Inc. All rights reserved.