Recent advances in understanding the structure and function of general transcription factor TFIID

Abstract

The general transcription factor TFIID is a macromolecular complex comprising the TATA-binding protein (TBP) and a set of 13-14 TBP associated factors (TAFs). This review discusses biochemical, genetic and electron microscopic data acquired over the past years that provide a model for the composition, organisation and assembly of TFIID. We also revisit ideas on how TFIID is recruited to the promoters of active and possibly repressed genes. Recent observations show that recognition of acetylated and methylated histone residues by structural domains in several TAFs plays an important role. Finally, we highlight several genetic studies suggesting that TFIID is required for initiation of transcription, but not for maintaining transcription once a promoter is in an active state.

Fig. 1

Structural organisation of yeast TFIID; (a, b) two opposite views of the TFIID complex showing the location of TAF1, TAF7 and TBP (white), TAF2 (blue) and a quasi symmetric core module (red). c Schematic representation of the TAF localisation within TFIID. The approximate positions of the subunits are derived from antibody-labelling experiments. The size of the spheres is proportional to the molecular mass of the proteins. Black lines represent documented protein–protein interactions of histone fold domain containing TAFs

Fig. 2

Schematic model for TFIID assembly. a The histone fold containing TAFs form heterodimers and associates with TAF5 to form the core complex. The ability of TAF5 to homodimerise is still open to question, and it is as yet unclear whether the histone-like heterodimers associate to form higher order ‘lobe’ structures in the absence of TAF5. b TAF5 and the histone-like heterodimers associate to form the core complex. Variants of this complex in the form of 5 TAF (Drosophila S2 cells), 7 TAF (baculovirus reconstitution in vitro) or 9 TAF (yeast in vivo) complexes have been described and are discussed in the text. c The core complex interacts with the TAF1-TAF7-TBP sub-module to form TFIID. TAF2 may associate independently with TFIID through interaction with TAF1, but may not be always present in TFIID

Fig. 3

Function of TFIID. a In wild-type cells TFIID is recruited along with pol II and the general transcription factors to facilitate PIC formation and promoter activation following mitosis or upon developmental cues. The transcriptional activators (Act), mediator complex (Med), TBP and TAFs, RNA pol II and the other general transcription factors (Pol II + GTFs) are all schematically depicted. b In normal cells, TFIID remains associated with the active promoter during the reinitiation step. c Following genetic inactivation of TBP or TAF10, the promoter remains in an active state until mitosis when the PIC is disassembled upon chromatin condensation and is unable to reform at the next interphase. Post-mitotic cells are unable to activate new sets of genes upon developmental cues or in response to signalling pathways. While inactivation of TAF10 has been shown to lead to loss TBP and TAFs at active promoters, it is not yet known whether TAFs remain at promoters in the absence of TBP