Near-atomic resolution visualization of human transcription promoter opening

Yuan He (), Chunli Yan, Jie Fang, Carla Inouye, Robert Tjian, Ivaylo Ivanov and Eva Nogales ()
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Yuan He: Lawrence Berkeley National Laboratory
Chunli Yan: Center for Diagnostics and Therapeutics, Georgia State University
Jie Fang: Howard Hughes Medical Institute, University of California
Carla Inouye: Li Ka Shing Center for Biomedical and Health Sciences, University of California
Robert Tjian: Howard Hughes Medical Institute, University of California
Ivaylo Ivanov: Center for Diagnostics and Therapeutics, Georgia State University
Eva Nogales: Lawrence Berkeley National Laboratory

Nature, 2016, vol. 533, issue 7603, 359-365

Abstract: Abstract In eukaryotic transcription initiation, a large multi-subunit pre-initiation complex (PIC) that assembles at the core promoter is required for the opening of the duplex DNA and identification of the start site for transcription by RNA polymerase II. Here we use cryo-electron microscropy (cryo-EM) to determine near-atomic resolution structures of the human PIC in a closed state (engaged with duplex DNA), an open state (engaged with a transcription bubble), and an initially transcribing complex (containing six base pairs of DNA–RNA hybrid). Our studies provide structures for previously uncharacterized components of the PIC, such as TFIIE and TFIIH, and segments of TFIIA, TFIIB and TFIIF. Comparison of the different structures reveals the sequential conformational changes that accompany the transition from each state to the next throughout the transcription initiation process. This analysis illustrates the key role of TFIIB in transcription bubble stabilization and provides strong structural support for a translocase activity of XPB.

Date: 2016
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DOI: 10.1038/nature17970

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