TATA box-binding protein (TBP)-related factor 2 (TRF2), a third member of the TBP family

Abstract

The TATA box-binding protein (TBP) is an essential component of the RNA polymerase II transcription apparatus in eukaryotic cells. Until recently, it was thought that the general transcriptional machinery was largely invariant and relied on a single TBP, whereas a large and diverse collection of activators and repressors were primarily responsible for imparting specificity to transcription initiation. However, it now appears that the ''basal'' transcriptional machinery also contributes to specificity via tissue-specific versions of TBP-associated factors as well as a tissue-specific TBP-related factor (TRF1) responsible for gene selectivity in Drosophila. Here we report the cloning of a TBP-related factor (TRF2) that is found in humans, Drosophila, Caenorhabditis elegans, and other metazoans. Like TRF1 and TBP, TRF2 binds transcription factor IIA (TFIIA) and TFIIB and appears to be part of a larger protein complex. TRF2's primary amino acid structure suggests divergence in the putative DNA binding domain, and not surprisingly, it fails to bind to DNA containing canonical TATA boxes. Most importantly, TRF2 is associated with loci on Drosophila chromosomes distinct from either TBP or TRF1, so it may have different promoter specificity and regulate a select subset of genes. These findings suggest that metazoans have evolved multiple TBPs to accommodate the vast increase in genes and expression patterns during development and cellular differentiation.

TRF2: TRansForming the view of general transcription factors

“…59 TRF2 is the TRF protein with the least similarity to TBP. [60][61][62][63][64][65] In 1999-2000, when different research groups have cloned TRF2 from multiple species, different names were coined. The name TRF2 was used for Drosophila 64 and humans, 65 as it followed the discovery of TRF1 in Drosophila.…”

“…The long TRF2 has only been identified in Drosophila. The short TRF2, which is highly conserved in evolution, 45,55,61,64,69,70 has been extensively studied and will henceforth be referred to as TRF2. The TRF2 core domain shows 40% identity and 60% similarity to the TBP core domain.…”

“…The TRF2 core domain shows 40% identity and 60% similarity to the TBP core domain. 64 Despite the homology between the TRF2 and TBP core domains, the TATA-interacting Phe residues of TBP are not conserved in TRF2, and indeed TRF2 cannot bind the TATAbox. 61,64,70 Hence, the variety of TBP-related factors adds another level of complexity to the regulation of transcription.…”

“…64 Despite the homology between the TRF2 and TBP core domains, the TATA-interacting Phe residues of TBP are not conserved in TRF2, and indeed TRF2 cannot bind the TATAbox. 61,64,70 Hence, the variety of TBP-related factors adds another level of complexity to the regulation of transcription. As discussed below, recent evidence suggests that TRF2 can direct RNAP II to subsets of TATA-less promoters and mediate diverse biological processes and transcriptional programs (Fig.…”

TBP, un facteur de transcription universel ?

“…En effet, trois protéines TRF1 (TBP-related factor 1), TLF (TBP-like factor)/TRF2 et TRF3 ont été identifiées et caractérisées [11][12][13][14][15][16][17]. La similarité entre ces protéines est limitée au domaine carboxyterminal conservé (Figure 2A-C …”