Developmental and transcriptional consequences of mutations in Drosophila TAF(II)60.
In vitro, the TAF(II)60 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 TAF(II)60 in metazoan transcription are not as clear. Here we have investigated the developmental and transcriptional requirements for TAF(II)60 by analyzing four independent Drosophila melanogaster TAF(II)60 mutants. Loss-of-function mutations in Drosophila TAF(II)60 result in lethality, indicating that TAF(II)60 provides a nonredundant function in vivo. Molecular analysis of TAF(II)60 alleles revealed that essential TAF(II)60 functions are provided by two evolutionarily conserved regions located in the N-terminal half of the protein. TAF(II)60 is required at all stages of Drosophila development, in both germ cells and somatic cells. Expression of TAF(II)60 from a transgene rescued the lethality of TAF(II)60 mutants and exposed requirements for TAF(II)60 during imaginal development, spermatogenesis, and oogenesis. Phenotypes of rescued TAF(II)60 mutant flies implicate TAF(II)60 in transcriptional mechanisms that regulate cell growth and cell fate specification and suggest that TAF(II)60 is a limiting component of the machinery that regulates the transcription of dosage-sensitive genes. Finally, TAF(II)60 plays roles in developmental regulation of gene expression that are distinct from those of other TAF(II) proteins.
Aoyagi
N
N
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Wassarman
D A
DA
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D019521:Body Patterning; D019070:Cell Lineage; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D017124:Conserved Sequence; D003433:Crosses, Genetic; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate / Q000196:embryology; D016133:Polymerase Chain Reaction; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013091:Spermatogenesis / Q000235:genetics; D035381:TATA-Binding Protein Associated Factors; D013997:Time Factors; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014921:Wings, Animal / Q000196:embryology
D029721:Drosophila Proteins; D012333:RNA, Messenger; D035381:TATA-Binding Protein Associated Factors; C084976:Taf6 protein, Drosophila; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase; D012319:RNA Polymerase II