Regulation of the initiation of eukaryotic transcription

DNA sequences that determine transcriptional regulation of a typical eukaryotic gene consist of a core promoter, which serves as a binding site for the GTF TFIID, and regulatory promoter or enhancer sequences, which bind transcriptional activators. The RNA polymerase II transcription machinery consists of over 50 proteins which are thought to bind to the core promoter in as few as two steps: binding of TFIIA-TFIID, followed by binding of a large pre-assembled holoenzyme complex consisting of the remaining GTFs, RNA polymerase II and associated regulatory proteins. Activators function to increase binding of the transcription machinery to the promoter in at least two ways: (i) simple protein-protein interactions with activators increases the affinity of the transcription machinery for the promoter, and (ii) some activators stabilize a conformation of the TFIIA-TFIID-DNA complex that enhances binding of the holoenzyme. Recent studies have identified many co-activators that function with activators to increase transcription by the RNA polymerase II transcription machinery. Although some co-activators may serve as bridges to connect activators with the transcription machinery, the mechanism of action of many co-activators has not yet been determined.