Publication Date:
2013-01-08
Description:
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 marks. TFIID is a megadalton-sized multiprotein complex composed of TATA-box-binding protein (TBP) and 13 TBP-associated factors (TAFs). 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 TFIID. A functional core-TFIID subcomplex was revealed in Drosophila nuclei, consisting of a subset of TAFs (TAF4, TAF5, TAF6, TAF9 and TAF12). 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 copy, 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 A 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bieniossek, Christoph -- Papai, Gabor -- Schaffitzel, Christiane -- Garzoni, Frederic -- Chaillet, Maxime -- Scheer, Elisabeth -- Papadopoulos, Petros -- Tora, Laszlo -- Schultz, Patrick -- Berger, Imre -- England -- Nature. 2013 Jan 31;493(7434):699-702. doi: 10.1038/nature11791. Epub 2013 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory Grenoble Outstation, Unit of Virus Host Cell Interactions UVHCI, UJF-CNRS-EMBL Unite Mixte International UMI 3265, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23292512" target="_blank"〉PubMed〈/a〉
Keywords:
Cells, Cultured
;
Cryoelectron Microscopy
;
HeLa Cells
;
Humans
;
*Models, Molecular
;
Protein Binding
;
Protein Structure, Tertiary
;
Transcription Factor TFIID/*chemistry/genetics/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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