title: Mutations in the histone fold domain of the TAF12 gene show synthetic lethality with the TAF1 gene lacking the TAF N-terminal domain (TAND) by different mechanisms from those in the SPT15 gene encoding the TATA box-binding protein (TBP).
abstract: The general transcription factor TFIID, composed of the TATA box-binding protein (TBP) and 14 TBP-associated factors (TAFs), is important for both basal and regulated transcription by RNA polymerase II. Although it is well known that the TAF N-terminal domain (TAND) at the amino-terminus of the TAF1 protein binds to TBP and thereby inhibits TBP function in vitro, the physiological role of this domain remains obscure. In our previous study, we screened for mutations that cause lethality when co-expressed with the TAF1 gene lacking TAND (taf1-DeltaTAND) and identified two DeltaTAND synthetic lethal (nsl) mutations as those in the SPT15 gene encoding TBP. In this study we isolated another nsl mutation in the same screen and identified it to be a mutation in the histone fold domain (HFD) of the TAF12 gene. Several other HFD mutations of this gene also exhibit nsl phenotypes, and all of them are more or less impaired in transcriptional activation in vivo. Interestingly, a set of genes affected in the taf1-DeltaTAND mutant is similarly affected in the taf12 HFD mutants but not in the nsl mutants of TBP. Therefore, we discovered that the nsl mutations of these two genes cause lethality in the taf1-DeltaTAND mutant by different mechanisms.
authors.affiliation: Division of Gene Function in Animals, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyake
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawaichi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kokubo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D005804:Genes, Lethal / Q000235:genetics; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics* / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000031:analogs & derivatives / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C106162:HFI1 protein, S cerevisiae; D006657:Histones; D009841:Oligonucleotides; C115017:SPT15 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C106785:TAF1 protein, S cerevisiae; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D035362:Transcription Factor TFIID