Repression of the transcriptional activity of ERR alpha with sequence-specific DNA-binding polyamides

摘要

The orphan nuclear receptors estrogen-related receptors (ERRs) bind to the estrogen-related receptor response element (ERRE) to regulate transcriptional programs in cellular metabolism and cancer cell growth. In this study, we evaluated the potential for a pyrrole-imidazole polyamide to block ERR alpha binding to ERREs to inhibit gene expression. We demonstrated that the ERRE-targeted polyamide 1 blocked the binding of ERR alpha to the consensus ERRE and reduced the transcriptional activity of ERR alpha in cell culture. We further showed that inhibiting ERR alpha transcriptional activity with polyamide 1 led to reduced mitochondrial oxygen consumption, a primary biological effect regulated by ERR alpha. Finally, our data demonstrated that polyamide 1 is an inhibitor for cancer cell growth.