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The TFIID transcription initiation complex is composed of TBP and multiple TAFs. Studies in unicellular systems indicate that TAF250 is required for progression through G1͞S of the cell cycle and repression of apoptosis. Here we extend these in vivo studies by determining the developmental requirements for TAF250 in a multicellular organism, Drosophila. TAF250 mutants were isolated in a genetic screen that also yielded TAF60 and TAF110 mutants, indicating that TAFs function coordinately to regulate transcription. Null alleles of TAF250 are recessive larval lethal. However, combinations of weak loss-of-function TAF250 alleles survive to adulthood and reveal requirements for TAF250 during ovary, eye, ocelli, wing, bristle, and terminalia development as well as overall growth of the fly. These phenotypes suggest roles for TAF250 in regulating the cell cycle, cell differentiation, cell proliferation, and cell survival. Finally, molecular analysis of TAF250 mutants reveals that the observed phenotypes are caused by mutations in a central region of TAF250 that is conserved among metazoan organisms. This region is contained within the TAF250 histone acetyltransferase domain, but the mutations do not alter the histone acetyltransferase activity of TAF250 in vitro, indicating that some other aspect of TAF250 function is affected. Because this region is not conserved in the yeast TAF250 homologue, TAF145, it may define an activity for TAF250 that is unique to higher eukaryotes. T FIID is a transcription initiation factor that nucleates the assembly of RNA polymerase II and other initiation factors (TFIIA, TFIIB, TFIIE, TFIIF, and TFIIH) at the core promoter of protein-coding genes (1). The most abundant form of Drosophila melanogaster TFIID is composed of TBP and eight TAFs: TAF250, TAF150, TAF110, TAF80, TAF60, TAF40, TAF30␣, and TAF30␤ (2). Similar stable multimeric TFIID complexes exist in all eukaryotic organisms investigated to date (3). In the yeast Saccharomyces cerevisiae, almost all TAFs are essential for viability (4). In Drosophila, TAF40, TAF60, and TAF110, the only TAFs that have been examined, are recessive embryonic or larval lethal and cell lethal, indicating the critical role that TAFs play in vivo (5, 6). However, it remains to be determined whether all TAFs or only subsets of TAFs are required for the transcription of TAF-dependent genes in vivo, whether TAFs are required for developmental events that are particular to multicellular organisms, and whether biochemical activities attributed to TAFs in vitro are required in vivo.TAF250 (also designated TAF230 in Drosophila, CCG1 in humans, and TAF145͞135 in yeast), is required for progression through the G 1 ͞S boundary of the cell cycle. Mammalian or yeast cells carrying temperature-sensitive alleles of TAF250 arrest in G 1 at the nonpermissive temperature (7,8). Furthermore, following growth arrest, mammalian cells undergo apoptosis (9). In addition to serving as a scaffold on which other TAFs and TBP are assembled, TAF250 possesses enzymatic, promoter r...

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