Regulation of Gene Expression by Multiple Forms of TFIID and Other Novel TAFII-Containing Complexes

Abstract

Ear ly work employed in vitro t ranscr ipt ion react ions to character ize protein factors required for accura te t ranscr ipt ion by RNA polymerase II (Pol II). Chromatographica lly separable protein fract ions were tested for their ability to produce cor rect ly in it ia ted t ranscr ipt s from promoter DNA fragments [1–3]. These differen t chromatographic fract ions, which conta in dist inct act ivit ies, were shown to be required for basa l Pol II t ranscr ipt ion and designa ted genera l Pol II t ranscr ipt ion factors, TFIIs. After the in it ia l character iza t ion of these fract ions it was shown by using differen t footpr in t ing techniques tha t a factor presen t in the TFIID fract ions preferen t ia lly binds to the TATA box, a core element shared by many promoters. Subsequent ly it was shown tha t in it ia t ion of the t ranscr ipt ion by Pol II from a promoter region requires the sequence-specific binding of the TFIID complex to the promoter . Binding of TFIID is followed by the subsequent ordered in teract ions of the other basa l factors (TFIIA, TFIIB, TFIIE, TFIIF , TFIIH, and TFIIJ ) and Pol II to yield a product ive prein it ia t ion complex (PIC) [4 – 6]. In tense effor t s to pur ify the cor responding protein or protein complex(es) in the differen t mammalian TFIID act ivity-conta in ing fract ions to homogeneity were unsuccessfu l. A breakthrough came with the discovery tha t a simila r TATA box binding act ivity exist s in the yeast S accharom yces cerevisiae [7], bu t tha t th is act ivity could be isola ted as a single polypept ide of 27 kDa [8]. This observa t ion set the stage for clon ing of yeast TATA box binding protein (TBP) [9 –11]. The cloning of the gene encoding yeast TBP allowed the isola t ion of severa l TBP-encoding genes from other eukaryotes [12, 13]. The compar ison of the size of recombinant TBP with tha t of mammalian TFIID fract ions subsequent ly revea led tha t TFIID, or a t least a fract ion of the TFIID act ivity, is a t igh t ly associa ted protein complex composed of TBP and a number (10 –13) of TBP-associa ted factors (TAF IIs) [13–16]. The discovery tha t TBP is not only a component of the TFIID complex, but is a lso present in t ranscr ipt ion complexes funct ion ing in Pol I and III t ranscr ipt ion , placed TBP as a cent ra l player in t ranscr ipt ion [12, 17]. The fact tha t recombinant TBP can replace the huge mult iprotein complex, TFIID, in basa l Pol II t ranscr ipt ion react ions in vitro, but tha t in metazoan cells TBP does not seem to exist a lone and is a lways associa ted with mult iprotein complexes, st imula ted much in terest in the role of TAF IIs in t ranscr ipt ion regula t ion . Today most of the TFIID components from S . cerevisiae, Drosophila, and humans have been ident ified (Table 1) and par t ia lly character ized [16, 18 –20]. Here we review the roles of TFIID and other novel TAF II-conta in ing complexes in the regula t ion of class II gene expression . We emphasize in par t icu la r those findings tha t under line the rela t ively recent idea tha t many TAF II-conta in ing complexes, and not a single TFIID, play impor tan t roles in t ranscr ipt iona l regu la t ion .