On a roll for new TRF targets: Figure 1.

Abstract

In the early 1990s, one of us wrote in these pages a review entitled “TBP, a universal transcription factor?” (Hernandez 1993). At the time, it had become clear that the TATA-box-binding protein TBP was not a transcription factor exclusively involved in transcription from RNA polymerase II (pol II) promoters as had been thought before, but rather a factor involved in transcription by all three main types of eukaryotic nuclear RNA polymerases. In retrospect, however, the question mark at the end of the title was a wise touch! Indeed, shortly thereafter, the first TBP-related factor, TRF1, was described (Crowley et al. 1993). Since then, two more TRFs have been discovered (for review, see Berk 2000; Davidson 2003; Hochheimer and Tjian 2003), and it was found that some genes dispense with TBP and TRFs altogether (Wieczorek et al. 1998). This “expansion” of TBP into a TBP family of proteins begs the question of which promoters are targeted by which TBP family member. In this issue of Genes & Development, Isogai et al. (2007a) report that the TATA-less histone H1 promoter is regulated by TRF2. This provides a possible mechanism for earlier observations linking TRF2 with chromatin structure (Martianov et al. 2002; Kopytova et al. 2006). Furthermore, the identification by Isogai et al. (2007a) of a large number of TRF2-bound sites in the Drosophila genome helps to establish Drosophila TRF2 as a broadly used core-promoter factor. Among the three classes of TBP-related factors described so far, TRF2—also called TBP-like protein (TLP) or TBP-like factor (TLF)—is the only one to be widely present in metazoans (Ohbayashi et al. 1999; Kaltenbach et al. 2000; Veenstra et al. 2000). TRF1 has been found only in Drosophila and Anopheles (Crowley et al. 1993; Isogai et al. 2007b), and TRF3 is restricted to vertebrates (Persengiev et al. 2003). All three proteins contain a core domain related to the TBP C-terminal core domain, and some also contain variable Nand C-terminal domains.