Structural insights into preinitiation complex assembly on core promoters

Science. 2021 Apr 30;372(6541):eaba8490. doi: 10.1126/science.aba8490. Epub 2021 Apr 1.


Transcription factor IID (TFIID) recognizes core promoters and supports preinitiation complex (PIC) assembly for RNA polymerase II (Pol II)-mediated eukaryotic transcription. We determined the structures of human TFIID-based PIC in three stepwise assembly states and revealed two-track PIC assembly: stepwise promoter deposition to Pol II and extensive modular reorganization on track I (on TATA-TFIID-binding element promoters) versus direct promoter deposition on track II (on TATA-only and TATA-less promoters). The two tracks converge at an ~50-subunit holo PIC in identical conformation, whereby TFIID stabilizes PIC organization and supports loading of cyclin-dependent kinase (CDK)-activating kinase (CAK) onto Pol II and CAK-mediated phosphorylation of the Pol II carboxyl-terminal domain. Unexpectedly, TBP of TFIID similarly bends TATA box and TATA-less promoters in PIC. Our study provides structural visualization of stepwise PIC assembly on highly diversified promoters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Corticotropin-Releasing Hormone / genetics
  • Cryoelectron Microscopy
  • Cyclin-Dependent Kinases / chemistry
  • HEK293 Cells
  • Humans
  • Multiprotein Complexes / chemistry*
  • Phosphorylation
  • Promoter Regions, Genetic*
  • Protein Binding
  • Protein Domains
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • RNA Polymerase II / chemistry
  • Swine
  • Transcription Factor TFIID / chemistry*
  • Transcription Initiation, Genetic*
  • Urocortins / genetics


  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • Multiprotein Complexes
  • Proto-Oncogene Proteins
  • Transcription Factor TFIID
  • UCN3 protein, human
  • Urocortins
  • Corticotropin-Releasing Hormone
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Cyclin-Dependent Kinases
  • RNA Polymerase II