Molecular Cell
Volume 73, Issue 1, 3 January 2019, Pages 97-106.e4
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Article
Promoter Distortion and Opening in the RNA Polymerase II Cleft

https://doi.org/10.1016/j.molcel.2018.10.014Get rights and content
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Highlights

  • Promoter meltability defines requirement of TFIIH for initiation

  • DNA distortions are induced by clamp closure prior to DNA melting

  • The initially melted region is structurally pre-defined by DNA distortions

  • Clamp closure and DNA distortion are general features of multi-subunit RNAPs

Summary

Transcription initiation requires opening of promoter DNA in the RNA polymerase II (Pol II) pre-initiation complex (PIC), but it remains unclear how this is achieved. Here we report the cryo-electron microscopic (cryo-EM) structure of a yeast PIC that contains underwound, distorted promoter DNA in the closed Pol II cleft. The DNA duplex axis is offset at the upstream edge of the initially melted DNA region (IMR) where DNA opening begins. Unstable IMRs are found in a subset of yeast promoters that we show can still initiate transcription after depletion of the transcription factor (TF) IIH (TFIIH) translocase Ssl2 (XPB in human) from the nucleus in vivo. PIC-induced DNA distortions may thus prime the IMR for melting and may explain how unstable IMRs that are predicted in promoters of Pol I and Pol III can open spontaneously. These results suggest that DNA distortion in the polymerase cleft is a general mechanism that contributes to promoter opening.

Keywords

Transcription initiation
RNA polymerase II
promoter DNA opening
DNA melting
gene regulation
promoter sequence motifs
XPB
Ssl2
ATPase
translocase

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