TBP-like Factors Come into Focus

highlights). Similarly, TLFs have ‫081ف‬ amino acid do-Molecular Biology Institute mains that are about 60% similar to the core domain of Paul D. Boyer Hall TBPs, with identical or chemically similar amino acids at many equivalent positions (Figure 1, black and gray Los Angeles, California 90095 highlights). This sequence similarity suggests that a TLF core domain folds into a saddle-shaped structure similar The TATA box binding protein (TBP) has been called to the TBP core. But, as pointed out by Dantonel et al. the universal transcription factor. In eukaryotes, three (1999), the TLFs contain distinct, conserved amino acids different multisubunit nuclear RNA polymerases tran-at several positions that distinguish them from TBPs scribe three distinct classes of RNAs. RNA polymerase (Figure 1, yellow highlight). II (Pol II) transcribes protein-coding genes. RNA poly-The conserved differences between TLFs and TBPs merases I and III (Pol I and Pol III) transcribe ribosomal include amino acids that would likely alter the DNA bind-RNAs and small stable RNAs such as tRNAs, respec-ing specificity of TLFs compared to TBPs (Figure 2; tively. Each RNA polymerase requires distinct additional Dantonel et al., 1999; Patikoglou et al., 1999). Impor-general transcription factors to locate promoters and tantly, pairs of phenylalanines that intercalate between initiate transcription. TBP is the one general transcrip-base pairs 1 and 2, and 7 and 8 of the TATA box, bending tion factor required by all three RNA polymerases (Burley the DNA sharply at these positions in the TBP–TATA and Roeder, 1996). For Pol II, TBP binds directly to the box complex, are not conserved in TLFs (Figure 1, arrow-TATA box promoter element, where it nucleates assem-heads). Consistent with this, most reports indicate that bly of Pol II and general transcription factors TFIIA, B, recombinant human TLF fails to bind to TATA boxes TATA box interaction defines the transcription start site et al., 1999). On the other hand, very few of the con-and therefore the precise DNA sequence translated into served differences between TLFs and TBPs occur in protein. Furthermore, the affinity of TBP for a gene's amino acids of TBP involved in protein–protein interac-specific TATA box sequence contributes to promoter tions with TFIIA, TFIIB, or Pol II or Pol III TBP-associated strength, i.e., the frequency with which the gene is tran-factors (TAFs) (Figure 2; Bryant et al., 1996 and refer-scribed. Interestingly, recent genomic and cDNA se-ences therein; Shen et al., 1998; Dantonel et al.,1999). quencing has …