Transcription Activation by a PNA-Peptide Chimera in a Mammalian Cell Extract Original Research Article

Synthetic activators that mimic the ability of native transcription factors to recruit the RNA polymerase holoenzyme to specific promoters could, in principle, be constructed by joining a sequence-specific DNA binding moiety with a molecule able to bind the holoenzyme. We report here that a peptide nucleic acid (PNA)-peptide chimera is capable of activating transcription in vitro in a HeLa nuclear extract. Specifically, a promoter-targeted PNA alone acts as a strong inhibitor of basal transcription in a HeLa nuclear extract, presumably due to structural modification of the promoter. However, the fusion of a Gal80-binding peptide to the PNA, but not control peptides, reactivates transcription. The Gal80-binding peptide was selected solely on the basis of its ability to bind the yeast repressor.