The structural basis of gene initiation

The initiation of gene transcription in eukaryotes is tightly controlled at the promoter of each gene through the actions of the pre-initiation complex (PIC), a large multi-subunit composed of general transcription factors, and RNA polymerase II (Pol II) assembles at the promoter to ensure correct loading of Pol II and opening of the duplex DNA for transcription into RNA. Two papers published in this issue report detailed cryo-electron microscopy structures of the Pol II machinery at near-atomic resolution. Eva Nogales and colleagues present structural models of the human PIC at all major steps during transcription initiation at near-atomic resolution. They provide new mechanistic insights into the processes of promoter melting and transcription bubble stabilization, as well as proposing an almost complete structural model of all of the PIC components bound to duplex DNA. Patrick Cramer and colleagues report structures of yeast initiation complexes containing all of the basal transcription factors except TFIIH, and containing either closed or open promoter DNA. They show that DNA opening can occur in the absence of TFIIH, and provide mechanistic insights into DNA opening and template-strand loading. The structures reveal the high structural conservation between yeast and human transcription initiation systems.