TRF1 (TBP-related factor 1) shows significant similarity to TBP with approximately 63% sequence identity in the carboxy-terminal core domain (D'Alessio et al. 2009; Akhtar et al. 2011; Müller et al. 2010). Consistent with this, TRF1 interacts with TFIIA, TFIIB, and the TATA box, and mediates basal transcription by RNAPII in vitro. Furthermore, it can also direct transcription from the TC box-containing “upstream” promoter of the tudor gene in vivo. Remarkably, transcription from the TATA-containing “downstream” promoter of this gene is not directed by TRF1 but instead by TBP/TFIID. These observations indicate that TRF1 could function as a core promoter selectivity factor in living cells.
TRF1 was originally identified in Drosophila and currently appears to be specific to insects. Importantly, TRF1 forms a complex with BRF1 and mediates transcription by RNAPIII in vitro as well as in vivo. This is in stark contrast to other species in which TFIIIB containing BRF1 and TBP (instead of TRF1) mediates transcription by RNAPIII. In addition, TRF1 also forms a large complex (>500 kDa) with a set of nTAFs (neuronal TRF1-associated factors) that are different from the TAFs in TFIID. This TRF1-nTAF complex may be involved in the transcription of a subset of class II (i.e., RNAPII-transcribing) genes, including tudor, as described above. TRF1 is expressed ubiquitously but is especially enriched in the central nervous system and gonads during the early stages of development, suggesting a tissue-specific function.