Disease relevance of SPT3

• Consistent with an effect on SAGA, nuclear expanded polyglutamine enhanced the toxicity of a deletion in the SAGA component SPT3 [1].

High impact information on SPT3

• Finally, we provide evidence that a specific interaction between Spt3 and TBP in vivo is important for Gal4 transcriptional activation at a step after SAGA recruitment [2].
• We found that remodeling was dependent on two SAGA complex components, Gcn5 and Spt3 [3].
• Most importantly, we showed that the involvement of Spt3 in chromatin remodeling was independent of transcription, as it was also observed for a nonpromoter nucleosome located next to an activator-binding site [3].
• Representatives of the SAGA pathway include the TATA binding protein, Spt3, and Mot1 [4].
• Furthermore, the association of Srb9 with the GAL1 upstream activation sequence requires SAGA and specifically Spt3 [5].

Biological context of SPT3

• Finally, overexpression of SPT3 caused a weak Not- mutant phenotype in mot1-1 mutants [6].
• An SPT3 deletion severely compromises the PHO5 promoter and reduces the extent of transcriptional activation by diminishing the binding of the TATA binding protein to the promoter without, however, affecting the rate or the extent of chromatin remodeling [7].
• We believe that, taken together, these data suggest that Spt3, Mot1, and TFIIA cooperate to regulate TBP-DNA interactions, perhaps at the level of TATA box selection in vivo [8].
• Ty transcription in an spt3-101 strain could be reestablished by introduction of the pGTyH3 plasmid, in which transcription of the Ty element TyH3 is under the control of the GAL1 promoter; these plasmid-derived Ty transcripts were SPT3-independent [9].
• The SPT3 gene is essential for Ty transposition, because transposition of chromosomal Ty elements ceased when the SPT3 gene was replaced with the frameshift mutation spt3-101 [9].

Physical interactions of SPT3

• Evidence that Spt3 functionally interacts with Mot1, TFIIA, and TATA-binding protein to confer promoter-specific transcriptional control in Saccharomyces cerevisiae [8].

Regulatory relationships of SPT3

• This genetic analysis has shown that an spt8 deletion mutation is suppressed by particular spt3 alleles [10].
• Third, increasing the dosage of NOT1 specifically inhibited the ability of spt15-122 to suppress the his4-912delta insertion but did not affect the Spt- phenotype of spt3 or spt10 at this locus [11].
• Importantly, the synthetic lethality for some of the TBP mutations is suppressed by a multicopy plasmid with SNR6 or by an spt3 mutation [12].

Other interactions of SPT3

• I also demonstrate specific genetic interactions between the Not complex, Mot1p, and another global regulator of transcription in S. cerevisiae, Spt3p [6].
• The Saccharomyces cerevisiae SPT8 gene encodes a very acidic protein that is functionally related to SPT3 and TATA-binding protein [10].
• These phenotypes are also similar to those caused by mutations in the SPT3 gene, which encodes a protein that directly interacts with TBP [10].
• We conclude from these experiments that the regulatory pathways in which RSP5 and SPT3 operate in yeast cells are conserved in higher eukaryotes [13].
• Inhibition of TATA-binding protein function by SAGA subunits Spt3 and Spt8 at Gcn4-activated promoters [14].

References