E2F1‐mediated transcriptional inhibition of the plasminogen activator inhibitor type 1 gene

摘要: 1Gene expression of the plasminogen activation system is cell-cycle dependent. Previously, we showed that ectopic E2F1 repressed activator inhibitor type 1 (PAI-1) promoter in a manner dependent on presence DNA-binding and transactivation domains but independent binding to pocket-binding proteins, suggesting novel mechanism for E2F-mediated negative gene regulation [Koziczak, M., Krek, W. & Nagamine, Y. (2000) Mol. Cell. Biol.20, 2014–2022]. However, it remains be seen whether endogenous E2F can exert similar effect. We report here down-regulation PAI-1 correlates with an increase activity. When cells were treated cdk2/4-specific inhibitor, which maintains inactive state, decline serum-induced mRNA levels was suppressed. In mutant U2OS expressing temperature-sensitive retinoblastoma protein (pRB), shift permissive temperature induced expression. stably E2F1-estrogen receptor chimeric could activated by tamoxifen, transcription markedly reduced tamoxifen even cycloheximide. These results all indicate directly repress gene. DNase I hypersensitive-site analysis suggested involvement conformation changes chromatin structure promoter. 5′ deletion multiple sites responsible regulation, some Interestingly, one these p53-binding element.