TATA Box Mimicry by TFIID Autoinhibition of Pol II Transcription

TATA Box Mimicry by TFIID: Minireview Autoinhibition of Pol II Transcription with formation of a stable TBP-TATA element complex. Deletion studies with dTAF II 230 mapped the autoinhibi-tory activity to the first 81 amino acids (reviewed in Liu In eukaryotes, RNA polymerase II (pol II) is responsible for transcribing nuclear genes encoding the messenger RNAs and several small nuclear RNAs. Like RNA poly-merases I and III, pol II cannot recognize its target promoter directly and initiate transcription in the absence of accessory proteins. Instead, this large multisubunit enzyme relies on both general transcription factors, or GTFs, and transcriptional activators and cofactors (both positive and negative) to regulate transcription from class II promoters. The primary DNA anchor of this complicated macromolecular machine is transcription factor IID, or TFIID, a 700 kDa complex composed of the TATA box–binding protein (TBP) and a set of phylogenetically conserved, pol II–specific TBP-associated factors, or TAFIIs (reviewed in Burley and Roeder, 1996). DNA binding by human TFIID was first demonstrated with the adenovirus major late promoter (AdMLP). DNase I foot-printing studies of the AdMLP and selected human gene promoters revealed sequence-specific interactions between human TFIID and the TATA element, which are primarily mediated by TBP (reviewed in Patikoglou and Burley, 1997). In contrast, protection both upstream and downstream of the TATA box is largely sequence independent , displays a nucleosome-like pattern of DNase I hypersensitivity, varies radically among promoters, and can be induced by some activators (reviewed in Burley and Roeder, 1996). In vivo, the transcription initiation process can be usefully divided into two mechanistic phases, referred to as antirepression and net activation (Figure 1A). At any given time, most class II nuclear genes are transcription-ally silent or repressed. Like activation (reviewed in Roeder, 1996), the mechanisms underlying transcriptional repression and its reversal are manifold. The subject of this minireview is an elegant autoinhibitory strategy characterized at the molecular level by the laboratories of Ikura and Nakatani using NMR spectroscopy (Liu et al., 1998 [this issue of Cell]). Their technically impressive structure determination proves that the N-terminal portion of the largest pol II–specific Drosophila melanogas-ter TBP-associated factor (dTAF II 230) recognizes the DNA-binding surface of Saccharomyces cerevisiae TBP, forming a stable 1:1 complex that inhibits TATA box binding (see Figure 6 in (Liu et al., 1998). Evidence for autoinhibition of TATA element recognition by TFIID first Figure 1. Autoinhibition of TFIID emerged nearly a decade ago, …