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.

Keywords: RNA polymerase II; TBP; TRF2; bilateria; evolution; regulatory systems.

Figure 1.

Evolution of the TRF2-based transcription system facilitated the emergence of complex animal body plans. (A) Alignment of TBP and TBP-related factors from Archaea (a), Drosophila (d), and humans (h). The TATA-box-interacting Phe residues that are mutated in TRF2 are indicated with arrows. The amino acid numbers are those of human TBP. The full amino acid sequences of the repeated core domains of these proteins are given in Supplemental Figure S1. (B) TRF2 emerged from a previously duplicated TBP protein prior to the evolution of bilateria and subsequent to the evolutionary split between bilaterians and nonbilaterian animals. A phylogenetic tree showing the presence or absence of TRF2 in selected metazoa is shown in Supplemental Figure S3.

Figure 2.

Postulated model for the evolution of the TRF2-based transcription system. We use TBP* as a general notation for a TBP-related protein that contains all four of the TATA-box-interacting Phe residues. The TBP system comprises the RNA Pol II TATA box program, the RNA Pol I and RNA Pol III transcriptional programs, and probably other programs. The TRF2 system includes the TCT and DPE transcriptional programs and probably other programs, such as one that transcribes histone H1 genes. The DPE functions with the Inr but not with the TCT motif (Parry et al. 2010; Kadonaga 2012). Therefore, the TCT and DPE transcriptional programs are distinct. TBP binds directly to the TATA-box motif, whereas purified TRF2 does not appear to bind to the TATA box or any other specific DNA sequence. Because of this difference in the DNA-binding properties of TBP and TRF2, these two system factors can function somewhat independently of each other. This facilitated the evolution of two distinct transcriptional systems.

Figure 3.

Model of TBP and TRF2 as system factors with their associated transcriptional programs. We postulate that the emergence of TRF2, which does not bind to the TATA box, provided a new and somewhat independent TRF2-based transcription system that could function in addition to the pre-existing TBP-based system. We propose that this arrangement led to new transcriptional programs that facilitated triploblasty and the evolution of bilateria.