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The architecture of human general transcription factor TFIID core complex


The initiation of gene transcription by RNA polymerase II is regulated by a plethora of proteins in human cells. The first general transcription factor to bind gene promoters is transcription factor IID (TFIID). TFIID triggers pre-initiation complex formation, functions as a coactivator by interacting with transcriptional activators and reads epigenetic marks1,2,3. TFIID is a megadalton-sized multiprotein complex composed of TATA-box-binding protein (TBP) and 13 TBP-associated factors (TAFs)3. Despite its crucial role, the detailed architecture and assembly mechanism of TFIID remain elusive. Histone fold domains are prevalent in TAFs, and histone-like tetramer and octamer structures have been proposed in TFIID4,5,6. A functional core-TFIID subcomplex was revealed in Drosophila nuclei, consisting of a subset of TAFs (TAF4, TAF5, TAF6, TAF9 and TAF12)7. These core subunits are thought to be present in two copies in holo-TFIID, in contrast to TBP and other TAFs that are present in a single copy8, conveying a transition from symmetry to asymmetry in the TFIID assembly pathway. Here we present the structure of human core-TFIID determined by cryo-electron microscopy at 11.6 Å resolution. Our structure reveals a two-fold symmetric, interlaced architecture, with pronounced protrusions, that accommodates all conserved structural features of the TAFs including the histone folds. We further demonstrate that binding of one TAF8–TAF10 complex breaks the original symmetry of core-TFIID. We propose that the resulting asymmetric structure serves as a functional scaffold to nucleate holo-TFIID assembly, by accreting one copy each of the remaining TAFs and TBP.

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Figure 1: Structure of the human TFIID core complex.
Figure 2: Molecular organization of conserved TAF domains.
Figure 3: Asymmetric 7TAF structure.
Figure 4: Model for holo-TFIID assembly.

Accession codes

Data deposits

The cryo-EM maps have been deposited in the 3D-EM database (EMBL-European Bioinformatics Institute). EMBD accession codes are EMD-2229 (3TAF), EMD-2230 (core-TFIID) and EMD-2231 (7TAF).


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We thank all members of the Berger, Schultz and Tora laboratories for advice and discussions. We are grateful to C. Romier for providing the X-ray structure of the TAF6 C-terminal domain before publication. We thank J. Demmers for mass spectrometric analyses and F. Grosveld for discussions. The EMBL, IBS and IGBMC core facilities are acknowledged for services. We are indebted to G. Schoehn for maintaining the electron microscopes in Grenoble. T. J. Richmond is acknowledged for advice and support. C.B. is a fellow of the joint European Commission (EC)/EMBL interdisciplinary research opportunities program (EIPOD). C.S. is recipient of a European Research Council (ERC) Starting Grant and an Agence Nationale de la Recherche (ANR) Jeunes Chercheuses award. I.B. acknowledges support from the EC Marie Curie Action and the EC Framework Programme (FP) 7 projects INSTRUCT, PCUBE, BioSTRUCT-X, 4D-CellFate and ComplexINC. P.S. acknowledges support from the Institut National de la Santé et de la Recherche Médicale (INSERM), the Centre National pour la Recherche Scientifique (CNRS), the Association pour la Recherche sur le Cancer (ARC) and the Fondation pour la Recherche Médicale (FRM). This work was supported by the ANR Projets Blancs puzzle-fit (to P.S.), ChromAct (to P.S. and L.T.) and TFIID-Complexes (to L.T., P.S. and I.B.).

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Authors and Affiliations



P.S., L.T. and I.B. designed the study; C.B., F.G. and I.B. implemented the MultiBac system; C.B., F.G. and M.C. produced, purified and characterized all TAF complexes; C.S. implemented gradient centrifugation and GraFix, analysed negative-stain electron microscopy data and calculated two-dimensional class averages; G.P. and P.S. carried out random conical tilt experiments, collected and analysed cryo-EM data of all complexes, and calculated and refined the electron microscopy densities; G.P. prepared the core-TFIID molecular structure by fitting crystal coordinates and homology models; E.S., L.T. and P.P. prepared and analysed endogenous TFIID for protein content. L.T. provided the anti-TAF10 antibody (mAb6TA). P.S., L.T. and I.B. supervised the work. G.P., C.B., P.S., L.T. and I.B. prepared the figures and wrote the manuscript together.

Corresponding authors

Correspondence to Patrick Schultz or Imre Berger.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, Supplementary Tables 1-3, Supplementary Text, Supplementary Figures 1-15 and Supplementary References. (PDF 4507 kb)

Human core-TFIID structure in an animated view

This video shows the core-TFIID cryo-EM structure (grey mesh), with the assigned TAF domains, crystal structures and homology models superimposed (color code as in Figure 1). Core-TFIID rotates around 360° in the video, illustrating the structure (MPEG-4 (H.264)). (MP4 13944 kb)

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Bieniossek, C., Papai, G., Schaffitzel, C. et al. The architecture of human general transcription factor TFIID core complex. Nature 493, 699–702 (2013).

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