2. Academic Validation
  3. Near-atomic resolution visualization of human transcription promoter opening

Near-atomic resolution visualization of human transcription promoter opening

  • Nature. 2016 May 19;533(7603):359-65. doi: 10.1038/nature17970.
Yuan He 1 2,  Chunli Yan 3,  Jie Fang 4,  Carla Inouye 5,  Robert Tjian 4 5 6,  Ivaylo Ivanov 3,  Eva Nogales 1 4 6
Affiliations

Affiliations

  • 1 Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
  • 2 Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA.
  • 3 Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30302, USA.
  • 4 Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
  • 5 Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, California 94720, USA.
  • 6 Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
PMID: 27193682 DOI: 10.1038/nature17970
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.

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