A NONNATURAL TRANSCRIPTIONAL COACTIVATOR

In eukaryotes, sequence-specific DNA-binding proteins activate gene ex pression by recruiting the transcriptional apparatus and chromatin rem odeling proteins to the promoter through protein-protein contacts. In many instances, the connection between DNA-binding proteins and the tr anscriptional apparatus is established through the intermediacy of ada pter proteins known as coactivators. Here we describe synthetic molecu les with low molecular weight that act as transcriptional coactivators . We demonstrate that a completely nonnatural activation domain in one such molecule is capable of stimulating transcription in vitro and in vivo. The present strategy provides a means of gaining external contr ol over gene activation through intervention using small molecules.