Developmental and Transcriptional Consequences of Mutations in Drosophila TAFII60

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American Society for Microbiology

RESUMO

In vitro, the TAFII60 component of the TFIID complex contributes to RNA polymerase II transcription initiation by serving as a coactivator that interacts with specific activator proteins and possibly as a promoter selectivity factor that interacts with the downstream promoter element. In vivo roles for TAFII60 in metazoan transcription are not as clear. Here we have investigated the developmental and transcriptional requirements for TAFII60 by analyzing four independent Drosophila melanogaster TAFII60 mutants. Loss-of-function mutations in Drosophila TAFII60 result in lethality, indicating that TAFII60 provides a nonredundant function in vivo. Molecular analysis of TAFII60 alleles revealed that essential TAFII60 functions are provided by two evolutionarily conserved regions located in the N-terminal half of the protein. TAFII60 is required at all stages of Drosophila development, in both germ cells and somatic cells. Expression of TAFII60 from a transgene rescued the lethality of TAFII60 mutants and exposed requirements for TAFII60 during imaginal development, spermatogenesis, and oogenesis. Phenotypes of rescued TAFII60 mutant flies implicate TAFII60 in transcriptional mechanisms that regulate cell growth and cell fate specification and suggest that TAFII60 is a limiting component of the machinery that regulates the transcription of dosage-sensitive genes. Finally, TAFII60 plays roles in developmental regulation of gene expression that are distinct from those of other TAFII proteins.

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