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

The TATA box-binding protein (TBP) is an essential component of the RNA pol ymerase II transcription apparatus in eukaryotic cells. Until recently, it was thought that the general transcriptional machinery was largely invarian t and relied on a single TBP, whereas a large and diverse collection of act ivators and repressors were primarily responsible for imparting specificity to transcription initiation. However, it now appears that the "basal" tran scriptional machinery also contributes to specificity via tissue-specific v ersions of TBP-associated factors as well as a tissue specific TBP-related factor (TRF1) responsible for gene selectivity in Drosophila, Here we repor t the cloning of a TBP-related factor (TRF2) that is found in humans, Droso phila, 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 div ergence in the putative DNA binding domain, and not surprisingly, it fails to bind to DNA containing canonical TATA boxes. Most importantly, TRF2 is a ssociated with loci on Drosophila chromosomes distinct from either TBP or T RF1, so it may have different promoter specificity and regulate a select su bset of genes. These findings suggest that metazoans have evolved multiple TBPs to accommodate the vast increase in genes and expression patterns duri ng development and cellular differentiation.