Enzymatic Activities of TFIID

The TAF1 component of TFIID possesses multiple enzymatic activities that are able to covalently modify histone tails and thus facilitate the reconfiguration of the chromatin structure in order to overcome nucleosome-mediated repression. TAF1 is known to function as an acetyltransferase in acetylating histones H3 and H4 (Mizzen et al., 1996), as a kinase in phosphorylating histone H2B (Maile et al., 2004), and as a histone-specific ubiquitin-activating/conjugating enzyme in mediating monoubiquitination of linker histone HI (Pham and Sauer, 2000). These histone-modifying activities indicate that TFIID may be specifically needed for transcription from nucleosome-embedded promoters. Indeed, only TFIID, but not TBP, can work in conjunction with a TFIID-deficient pol II holoenzyme complex (see Fig.2.2 in the Chapter by Hou and Chiang) to facilitate activator-dependent transcription from an in vi'fro-reconstituted chromatin template, suggesting a unique involvement of TAFs in chromatin transcription

(Wu et al., 1999). The importance of the acetyltransferase activity of TAF1 for gene transcription has also been demonstrated for MHC class I genes, where suppression of TAF 1 enzymatic activity by TAF 1-interacting protein TAF7 leads to inhibition of transcription (Gegonne et al., 2001). Similar to other histone acetyltransferases (HATs), TAF1 contains two tandem bromodomains recognizing acetylated lysine 14 (K14) of histone H3 as well as acetylated K5, K8, K12, and K16 of histone H4 (Jacobson et al., 2000; Kanno et al., 2004). This bromodomain-mediated interaction likely enhances TFIID binding to acetylated promoters previously modified by activator-recruited HATs. The structure of the human TAF1 double bromodomain spanning amino acid residues 1359-1638, resolved by X-ray crystallography at 2.1Ä resolution, reveals that two acetylated lysine residues of histone H4, separated by 7 or 8 amino acids (i.e., K5/K12 or K8/K16), are preferentially recognized by the double bromodomain, where the Ni:-acetyllysinc-binding pocket is situated within the amino acid residues of the two loops connecting the four antiparallel a-helices that constitute the core of each bromodomain (Jacobson et al., 2000).

Other than acting on histones, TAF1, as a free entity or part of TFIID, can also covalently modify other general transcription factors and cofactors, as demonstrated by acetylation on TFIIEp (Imhof et al., 1997), phosphorylation on RAP74 (Dikstein et al., 1996), PC4 (Kershnar et al., 1998; Malik et al., 1998), and the P subunit of TFIIA (Solow et al., 2001), and presumably ubiquitination on TAF5 and itself as well (Auty et al., 2004).

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