The canonical mechanism of transcription initiation in all metazoans involves recruitment of TATA-binding proteins (TBP, TLF or TBP2 in vertebrates) to the promoter, as a rate-limiting step before binding of RNA polymerase II. TBP, TLF and TBP2 have non-redundant functions, but the degree of redundancy between them is not clear; nor is it well understood whether there are TBP-independent mechanisms of transcription initiation in vivo. On p. , Gert Veenstra and co-workers now show that, during early Xenopus development, there is a small group of genes whose transcription is independent of all TBP family members (denoted TBP family-insensitive or TFI genes). These genes are enriched for factors expressed in mesoderm and at Spemann's organiser and include several key transcription factors involved in mesendoderm specification. Strikingly, most TFI genes are bound by these TFI transcription factors. Gcn5, a component of the SAGA complex thought be involved in non-canonical transcription initiation, is recruited to TFI promoters upon TBP family knockdown, is not required for their transcription in the presence of TBP-related factors, but seems to compensate in their absence. This work provides clear evidence that alternative mechanisms of transcription initiation exist in vivo, and that they may be preferentially used for a particular set of key developmental genes.
