Disease relevance of TAF1

• The phenotypes included a low steady-state level of the mutant TBP, transcriptional derepression, dominant slow growth (partial toxicity), and synthetic toxicity in combination with a deletion of the TAF1 TAND domain [1].

High impact information on TAF1

• The TAND domain of TAF1 plays a primary inhibitory role at very few genes, but its function becomes widespread when other TBP interactions are compromised [2].
• In contrast, levels of Taf1, TFIIB, and RNA polymerase II are reduced at Mot1-activated promoters in mot1 cells [3].
• Moreover, the N-terminal domain of TAF1 was mapped in lobe C, whereas the histone acetyltransferase domain resides in lobe A along with TAF7 [4].
• In similar experiments, we show that the anti-oestrogen, ICI 164,384, does not exhibit any oestrogenic activity and, therefore, acts always as a pure antagonist, even though it does not inhibit the activity of the isolated TAF-1 [5].
• Representatives of the TFIID pathway include the TATA binding protein, TAF1, and Bdf1 [6].

Biological context of TAF1

• Differential requirement of SAGA subunits for Mot1p and Taf1p recruitment in gene activation [7].
• Interestingly, histone acetylation at promoter regions throughout the genome does not require TAF1 or RNA polymerase II, indicating that most acetylation is likely to precede transcription and not depend upon it [8].
• The central role of the putative HAT-containing TAF1 subunit of TFIID in gene expression raises the fundamental question as to what extent, if any, TAF1 contributes to acetylation in vivo and to what extent it is redundant with other HATs [8].
• A similar mechanism may be responsible for phosphorylation of the C-terminal region of mammalian TAF1 [9].
• These mutants are impaired for dimerization, TAF1 TAND binding, and TATA binding to an extent that is consistent with the crystal or nuclear magnetic resonance structure of these or related interactions [1].

Anatomical context of TAF1

• Confocal microscopy showed that TAF1 colocalizes with UBF in Hela cells, and cell fractionation experiments provided further evidence that a portion of TAF1 is localized in the nucleolus, the organelle devoted to ribosomal DNA transcription [10].

Associations of TAF1 with chemical compounds

• After galactose induction of the TAF1 mutants and temperature-induced elimination of the resident Taf1ts2 protein, we examined the properties and phenotypes of the mutants, including their impact on genome-wide transcription [11].
• Ferrioxamine B was taken up preferentially via the products of the SIT1 gene and triacetylfusarinine C by the TAF1 gene product, but the specificity was not absolute [12].
• The gene YHL047c Sce (designated TAF1) was disrupted using the kanMX disruption module in a fet3 background (strain DEY 1394 delta fet3), possessing a defect in the high affinity ferrous iron transport [13].
• Furthermore, we show that in yeast the antagonistic effects of the antiestrogen nafoxidine arise from a modulation of the synergistic interactions of TAF-1 and TAF-2, and not simply from an inactivation of TAF-2 by antihormone [14].
• We also confirm that the agonistic activity of 4-hydroxytamoxifen (OHT) can be ascribed to the activity of TAF-1 [15].

Physical interactions of TAF1

• 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 [16].

Regulatory relationships of TAF1

• The N-terminal domain (TAND) of TAF1 protein (Taf1p) inhibits TBP by binding to its concave and convex surfaces [17].

Other interactions of TAF1

• TBP recruitment was compromised in two different mot1 mutant strains, but was only moderately affected in a taf1 Ts strain [18].
• Surprisingly, the deletion of GCN5 reduces Taf1p binding to both promoters [7].
• 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 [16].
• We isolated a temperature-sensitive nonsense allele of TAF1, taf1-4, which is synthetically lethal at the permissive temperature when combined with not4 and not5 mutants and which produces high levels of a C-terminally truncated yTAF1 derivative [19].
• Impaired core promoter recognition caused by novel yeast TAF145 mutations can be restored by creating a canonical TATA element within the promoter region of the TUB2 gene [20].

References