The architecture of human general transcription factor TFIID core complex

The structures of three distinct human transcription factor IID (TFIID) protein assemblies are solved using cryo-electron microscopy; by incorporating TAF8 and TAF10, the key structural changes that remodel TFIID during assembly are determined, particularly the transition from a symmetric core-TFIID to an asymmetric holo-complex. TFIID transcription factor core structure TFIID is the first general transcription factor to bind gene promoters prior to gene transcription by RNA polymerase II, triggering pre-initiation complex formation and functioning as a coactivator. TFIID is a large multiprotein complex composed of TATA-box-binding protein (TBP) and TBP-associated factors (TAFs). Imre Berger and colleagues now determine structures of three distinct human TFIID protein assemblies using cryo-electron microscopy. In their model for step-wise assembly of the complex, the transition from a symmetric core TFIID to an asymmetric holo-complex occurs upon binding of TAF8 and TAF10, which induces major conformational changes. 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 1 , 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 TFIID 4 , 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 copy 8 , 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 comp