Structural Superimposition

Abstact

Transcription initiation by RNA polymerase II (RNA Pol II) occurs next to a +1 nucleosome, which is positioned downstream of the transcription start site (TSS). The +1 nucleosome influences pre-initiation complex (PIC) assembly and RNA Pol II pausing, but its function in transcription initiation and the transition to elongation remains unclear. Here, we investigate the transcription initiation-elongation transition in vitro using DNA templates containing a +1 nucleosome and present cryo-electron microscopy (cryo-EM) structures of five intermediate states. First, after PIC assembly, ATP binding to TFIIH enables the +1 nucleosome to evict TFIID from the PIC. Following DNA opening, the +1 nucleosome stimulates TFIIH translocase activity and initial RNA synthesis. Finally, after DNA bubble rewinding, the +1 nucleosome removes TFIIH from the early elongation complex for promoter escape. Our findings show that the +1 nucleosome not only acts passively in PIC assembly and RNA Pol II pausing but rather has active functions during the initiation-elongation transition of transcription.