Considerations of transcriptional control mechanisms: do TFIID-core promoter complexes recapitulate nucleosome-like functions?

Abstract

The general transcription initiation factor TFIID was originally identified, purified, and characterized with a biochemical assay in which accurate transcription initiation is reconstituted with multiple, chromatographically separable activities. Biochemical analyses have demonstrated that TFIID is a multiprotein complex that directs preinitiation complex assembly on both TATA box-containing and TATA-less promoters, and some TFIID subunits have been shown to be molecular targets for activation domains in DNA-binding regulatory proteins. These findings have most commonly been interpreted to support the view that transcriptional activation by upstream factors is the result of enhanced TFIID recruitment to the core promoter. Recent insights into the architecture and cell-cycle regulation of the multiprotein TFIID complex prompt both a reassessment of the functional role of TFIID in gene activation and a review of some of the less well-appreciated literature on TFIID. We present a speculative model for diverse functional roles of TFIID in the cell, explore the merits of the model in the context of published data, and suggest experimental approaches to resolve unanswered questions. Finally, we point out how the proposed functional roles of TFIID in eukaryotic class II transcription fit into a model for promoter recognition and activation that applies to both eubacteria and eukaryotes.

Figure 1

States of gene expression. Within physiological chromatin, each class II gene may be present in any one of three states that thereby determines its capacity to be transcribed. (A) “Inactive” genes are packaged in nucleosomes and inaccessible to the transcription machinery. PIC assembly and initiation must be preceded by major chromatin remodeling that, in some cases, may require DNA synthesis and mitosis. (B) “Poised” genes contain TFIID bound to the core promoter region and thus are rapidly inducible though otherwise inactive. The conformation of this complex, in the absence of an inducing stimulus (activator) renders the promoter inaccessible to RNA polymerase II and other GTFs (or the holoenzyme). (C) “Active” genes contain promoter-bound activators that recruit RNA polymerase II and GTFs (or the holoenzyme) either (i) “indirectly,” by inducing a conformational change in the TFIID–core promoter complex that renders the initiation region accessible or (ii) “directly,” via protein–protein interactions with these components.

Figure 2

Universal aspects in transcription initiation mechanisms. (A) Initiation in eubacteria requires the binding of a sigma factor to the RNA polymerase (Pol) to form the holoenzyme. This event induces a conformational change in the sigma factor, enabling it to recognize specific sequences of proximal promoter elements, leading to transcription initiation. Activators may facilitate this recognition step through interactions with holoenzyme components. (B) Initiation on class II promoters may involve analogous steps of holoenzyme assembly with GTFs binding to RNA polymerase II (Pol II), depicted here to emphasize parallels to the eubacterial paradigm. This holoenzyme (or RNA polymerase II and unbound GTFs) is able to recognize the initiation region via TFIID, but only when TFIID is bound to the core promoter DNA in a particular conformation(s) and not in another(s). The transcriptionally active conformation of TFIID can be induced by a large variety of upstream-bound activators via the coactivator function of certain TAFs and soluble cofactors.