TRF2 and the evolution of the bilateria

Abstract

The development of a complex body plan requires a diversity of regulatory networks. Here we consider the concept of TATA-box-binding protein (TBP) family proteins as “system factors” that each supports a distinct set of transcriptional programs. For instance, TBP activates TATA-box-dependent core promoters, whereas TBP-related factor 2 (TRF2) activates TATA-less core promoters that are dependent on a TCT or downstream core promoter element (DPE) motif. These findings led us to investigate the evolution of TRF2. TBP occurs in Archaea and eukaryotes, but TRF2 evolved prior to the emergence of the bilateria and subsequent to the evolutionary split between bilaterians and nonbilaterian animals. Unlike TBP, TRF2 does not bind to the TATA box and could thus function as a new system factor that is largely independent of TBP. We postulate that this TRF2-based system served as the foundation for new transcriptional programs, such as those involved in triploblasty and body plan development, that facilitated the evolution of bilateria.

TRF2: TRansForming the view of general transcription factors

“…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.…”

“…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.…”

“…77 Recent analysis of Drosophila genes with high TRF2 occupancy revealed a strong relationship between TRF2 and processes such as cell differentiation and development. 70,73 An evolutionary conservation analysis indicated that TRF2 evolved by duplication of the TBP gene. 70 TRF2 is highly conserved in evolution and is present in all bilaterian organisms containing 3 germ layers: endoderm, mesoderm and ectoderm.…”

“…TRF2 was not found in any of the non-bilaterian genomes that are currently available. 70 As more ancient animals only contain 2 germ layers (endoderm and ectoderm) and the emergence of the bilateria was at the same evolutionary point as that of trf2, one can speculate that TRF2 is important for mesoderm formation. Notably, analysis of core promoter composition of Drosophila genes involved in embryonic development and differentiation reveals the prevalence of the DPE motif.…”

The human initiator is a distinct and abundant element that is precisely positioned in focused core promoters

“…There are no universal core promoter motifs. Specific core promoter elements can be important for enhancer-promoter specificity (for example, see Butler and Kadonaga 2001; Juven-Gershon et al 2008) as well as the regulation of gene networks (for example, see Juven-Gershon et al 2008;Parry et al 2010;Duttke et al 2014;Wang et al 2014).The long-term goal of this study is to gain a more specific understanding of the human core promoter. It has been estimated, for instance, that <25% of human core promoters contain the well-known TATA box or a TATA-like sequence (Gershenzon and Ioshikhes 2005;Carninci et al 2006;Yang et al 2007).…”