A TBPRelated Factors

All multicellular organisms contain at least two TBP genes encoding proteins sharing sequence homology at their C-terminal 180 amino acid core DNA-binding domains. While the first gene encodes TBP, considered a universal TATA-binding transcription factor present in all eukaryotes, the second gene encodes TBP-related factor 2 (TRF2), also called TBP-related protein (TRP), TBP-like factor (TLF) or TBP-like protein (TLP), recognizing a sequence element distinct from the TATA box due to some conserved amino acid changes, including those two phenylalanine residues that kink the TATA box, within the C-terminal core that shares -60% sequence homology and 41% identity with that of TBP (Dantonel et al., 1999; Berk, 2000; Hochheimer and Tjian, 2003). Interestingly, amino acid residues important for interactions with TFIIA and TFIIB remain mostly unaltered, allowing TRF2 to associate with TFIIA and TFIIB (Maldonado, 1999; Moore et al., 1999; Rabenstein et al., 1999; Teichmann et al., 1999) and thus assembling into a functional PIC able to transcribe some TATA-less promoters likely via undefined TRF2-binding elements (Ohbayashi et al., 2003; Chong et al., 2005). This property of TRF2 also enables it to function as a repressor preventing PIC formation initiated by TBP or TFIID on TATA-containing promoters (Moore et al., 1999; Teichmann et al., 1999; Chong et al., 2005). Not surprisingly, inactivation of TRF2 in C. elegans by RNA interference fails to support embryogenesis (Dantonel et al., 2000; Kaltenbach et al., 2000), indicating that TRF2 is essential for normal cell development.

Other than TRF2, two species-specific TRFs (TRF1 and TRF3) have also been identified. TRF1 (Crowley et al., 1993), so far only identified in neuronal and germ cells of Drosophila (reviewed in Berk, 2000; Hochheimer and Tjian, 2003), exhibits 63% amino acid sequence identity to TBP at its C-terminal DNA-binding core which maintains most of the conserved residues important for interactions with the TATA box, TFIIA and TFIIB (Rabenstein et al., 1999). It is thus not unexpected that TRF1 binds TFIIA and TFIIB and can partially substitute for TBP in directing pol II-dependent transcription from some TATA-containing promoters in vitro (Hansen et al., 1997). Interestingly, a TRF1 target gene, Tudor, whose expression is driven by two tandem promoters containing a TRF1-responsive upstream promoter and a TBP/TFIID-responsive downstream promoter, has been identified in Drosophila cells. A TC-rich sequence, located at ~25 nucleotides upstream of this TRF1-responsive Tudor promoter preferentially nucleates TRF1-mediated PIC assembly and transcription from the upstream Tudor promoter. In vivo, promoter selectivity by TRF1 is likely enhanced by some promoter-specific transcriptional activators or by its association with neuron-specific TRF1-associated factors (nTAFs) to form a multiprotein complex, distinct from TFIID (Holmes and Tjian, 2000). That TRF1 does not interact with TFIID-specific TAFs provides a rationale why TRF1 and TBP are not interchangeable at respective TRF1-responsive upstream and TBP-responsive downstream Tudor promoters (Holmes and Tjian, 2000).

TRF3, which shows 93% amino acid sequence identity to TBP at the C-terminal core region sharing the same sequence as TBP at all the conserved residues involved in TATA binding and interactions with TFIIA and TFIIB, is unique to vertebrates, ranging from fish to humans, but is not present in urochordate Ciona intestinalis and lower eukaryotes, such as Drosophila and C. elegans (Persengiev et al., 2003). Unlike TRF1 and TRF2, which are expressed only in selective tissues, TRF3 is ubiquitously expressed in every cell type examined, similar to that of TBP, and is present as a protein complex with a molecular size of approximately 200 kDa. Since TAF1 does not cofractionate with the TRF3 complex, it is likely that polypeptides constituting the TRF3 complex are different from TAFs defined in TFIID and nTAFs associated with TRF1. The transcriptional property of TRF3 and its regulated genes remain to be characterized.

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