Dissecting TFIID assembly

Association of the transcription factor TFIID with gene promoters drives the formation of the pre-initiation complex during RNA polymerase II-mediated transcription. TFIID consists of TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). How does the TFIID complex assemble? Previous studies in Drosophila melanogaster and yeast have led to a model in which a core-TFIID subcomplex forms initially that has twofold symmetry and contains duplicate copies of particular TAFs; addition of TBP and the remaining TAFs is thought to produce an asymmetric holo-TFIID. Here, Bieniossek et al. determine the structure of human core-TFIID complexes using wild-type or mutant TAFs and cryo-electron microscopy. Consistent with previous studies, they show that the core TFIID has twofold symmetry, and the authors were able to assign the conserved domains of the TAFs within this structure. They also provide insights into the transition of this complex to the asymmetric structure that is characteristic of the holo-TFIID by showing that the addition of one TAF8–TAF10 complex is sufficient to induce asymmetry. This supports a model of stepwise holo-TFIID assembly from the core-TFIID complex.