Mutations in TAF60 and TAF250 cause similar developmental defects in Drosophila. N. Aoyagi , E.M. Schlag , D.A. Wassarman. Cell Biol & Metabolism Branch, NICHD/NIH, Bethesda, MD.

   The TFIID transcription initiation complex is composed of TATA-box binding protein (TBP) and multiple TBP-associated factors (TAFs). TAFs have been implicated as transcriptional regulators of subsets of RNA polymerase II genes. Mutations in TAF60, TAF110 and TAF250 were identified in a genetic screen for modulators of Ras signaling during eye development (1).
   To investigate TAF60 requirements during developmental events that take place after the lethal phase of TAF60 mutants (late in embryogenesis), we have rescued the lethality by expression of a TAF60 transgene under control of a heat-shock inducible promoter. TAF60 rescued flies survive to adulthood and reveal requirements for TAF60 during ovary, eye, ocelli, wing, bristle, and terminalia development. Analysis of flies transheterozygous for two TAF250 alleles display similar phenotypes suggesting that TAF60 and TAF250 function coordinately to regulate transcription throughout Drosophila development.
   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 (HAT) domain, but the mutations do not alter the HAT activity of TAF250 in vitro, indicating that some other aspect of TAF250 function is affected. Since this region is not conserved in the yeast TAF250 homologue, TAF145, it may define an activity for TAF250 that is unique to higher eukaryotes.
   1. Karim et al. (1996) Genetics 143, 315.