The general transcription factor TFIID sets the mRNA start site and consists of TATA-binding protein and associated factors (TAF II s), some of which are also present in SPT-ADA-GCN5 (SAGA)-related complexes. In yeast, results of multiple studies indicate that TFIID-specific TAF II s are not required for the transcription of most genes, implying that intact TFIID may have a surprisingly specialized role in transcription. Relatively little is known about how TAF II s contribute to metazoan transcription in vivo, especially at developmental and tissuespecific genes. Previously, we investigated functions of four shared TFIID/SAGA TAF II s in Caenorhabditis elegans. Whereas TAF-4 was required for essentially all embryonic transcription, TAF-5, TAF-9, and TAF-10 were dispensable at multiple developmental and other metazoan-specific promoters. Here we show evidence that in C. elegans embryos transcription of most genes requires TFIID-specific TAF-1. TAF-1 is not as universally required as TAF-4, but it is essential for a greater proportion of transcription than TAF-5, -9, or -10 and is important for transcription of many developmental and other metazoan-specific genes. TAF-2, which binds core promoters with TAF-1, appears to be required for a similarly substantial proportion of transcription. C. elegans TAF-1 overlaps functionally with the coactivator p300/ CBP (CBP-1), and at some genes it is required along with the TBP-like protein TLF(TRF2). We conclude that during C. elegans embryogenesis TAF-1 and TFIID have broad roles in transcription and development and that TFIID and TLF may act together at certain promoters. Our findings imply that in metazoans TFIID may be of widespread importance for transcription and for expression of tissue-specific genes.Eukaryotic mRNA transcription involves formation of a preinitiation complex (PIC) 1 at the core promoter, which directs initiation. The PIC includes a set of general transcription factors (TFIIA, B, D, E, F, and H) and a mediator complex, along with RNA polymerase II (pol II) (1, 2). In Saccharomyces cerevisiae many PIC components have surprisingly specific roles at particular gene subsets (3, 4). Much less is known about how individual PIC components contribute to transcription regulation in metazoans, which have evolved a greater complexity of stage-and tissue-specific gene control and additional genes that are not present in yeast.The general transcription factor TFIID is of particular interest because it establishes the start site and provides enzymatic activities that may regulate transcription (5, 6). TFIID is comprised of the TATA-binding protein (TBP) along with ϳ14 TBP-associated factors (TAF II s). TAF II s interact with core promoter elements and contact a diverse array of upstream transactivators (5-8). TAF-1 and TAF-2 together bind directly to the initiator (Inr) element, which encompasses the start site (9). TAF-1, the largest TAF II , is also necessary for TFIID stability and possesses histone acetyltransferase, kinase, and ubiquitin conjugating activitie...