[A precise equilibrium equation for four steps of binding between TBP and TATA-box allows for the prediction of phenotypical expression upon mutation].
Among the main events of transcription initiation of TATA-containing genes in eukayotes are the recognition and binding of the TATA-box by the TATA-binding protein (TBP) to start the preinitiation complex formation on the nucleosomal DNA. Using the equilibrium equation for step-by-step TBP/TATA-binding, we have analyzed 69 experimental datasets on the characteristics of biologicacally important features altered by TATA-box mutations. Among these features, the TBP/TATA-complex parameters, the transcription level, the activity of gene products, yeast colony growth at a dose of growth inhibitor (phenotype), and the heterogenity of the response of a population to unspecific environmental stress have been described. Significant correlations were found between in silico prediction for TBP/TATA affinity and experimental data for in vivo and in vitro test-systems based on 15 cell types of 19 species, RNA polymerases II and III, and natural, recombinant or mutant TBP. Such an invariant impact of the step-by-step TBP/TATA-binding on the biological activity of complex systems, from a molecule to a population, might be due to the fact that TBP/TATA-complex formation precedes specific steps of transcription machinery assembly, which provide the multivariant jigsaw puzzle according to the expression pattern of each eukaryotic gene.
Ponomarenko
P M
PM
Suslov
V V
VV
Savinkova
L K
LK
Ponomarenko
M P
MP
Kolchanov
N A
NA
D000465:Algorithms; D000818:Animals; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D013312:Stress, Physiological; D016385:TATA Box; D035181:TATA-Box Binding Protein / Q000235:genetics*; D013754:Tetracyclines / Q000494:pharmacology; D014158:Transcription, Genetic; D015003:Yeasts / Q000187:drug effects / Q000235:genetics / Q000254:growth & development
D035181:TATA-Box Binding Protein; D013754:Tetracyclines; C016229:4-epianhydrotetracycline