Structures of transcription pre-initiation complex with TFIIH and Mediator

For transcription initiation, RNA polymerase (Pol) II assembles with general transcription factors on promoter DNA to form the pre-initiation complex (PIC). We report cryo-EM structures of the yeast PIC and PIC-core Mediator (cMed) complex at nominal resolutions of 4.7 Å and 5.8 Å, respectively. The structures reveal TFIIH and suggest how the TFIIH modules ‘core’ and ‘kinase’ function in promoter opening and Pol II phosphorylation, respectively. The TFIIH core subunit Ssl2 (human XPB) is positioned on downstream DNA by the ‘E-bridge’ helix in TFIIE, consistent with TFIIE-stimulated DNA opening. The TFIIH kinase module subunit Tfb3 (human MAT1) anchors the kinase Kin28 (human Cdk7) that is mobile in the PIC but preferentially located between the Mediator hook and shoulder in the PIC-cMed complex. Open spaces between the Mediator head and middle modules may allow access of the kinase to its substrate, the C-terminal domain (CTD) of Pol II.