Transcription factor concentrations versus binding site affinities in the yeast S. cerevisiae.
Transcription regulation is largely governed by the profile and the dynamics of transcription factors' binding to DNA. Stochastic effects are intrinsic to this dynamics, and the binding to functional sites must be controlled with a certain specificity for living organisms to be able to elicit specific cellular responses. Specificity stems here from the interplay between binding affinity and cellular abundance of transcription factor proteins, and the binding of such proteins to DNA is thus controlled by their chemical potential. We combine large-scale protein abundance data in the budding yeast with binding affinities for all transcription factors with known DNA binding site sequences to assess the behavior of their chemical potentials in an exponential growth phase. A sizable fraction of transcription factors is apparently bound non-specifically to DNA, and the observed abundances are marginally sufficient to ensure high occupations of the functional sites. We argue that a biological cause of this feature is related to its noise-filtering consequences: abundances below physiological levels do not yield significant binding of functional targets and mis-expressions of regulated genes may thus be tamed.
Aurell
Erik
E
Department of Computational Biology, KTH-Royal Institute of Technology, AlbaNova University Center, Stockholm, Sweden. eaurell@kth.se
d'Hérouël
Aymeric Fouquier
AF
Malmnäs
Claes
C
Vergassola
Massimo
M
D001665:Binding Sites; D001703:Biophysics / Q000379:methods*; D002453:Cell Cycle; D004247:DNA / Q000737:chemistry; D005656:Fungal Proteins; D015966:Gene Expression Regulation, Fungal; D008954:Models, Biological; D015233:Models, Statistical; D008962:Models, Theoretical; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D012984:Software; D014157:Transcription Factors / Q000378:metabolism*
D005656:Fungal Proteins; D014157:Transcription Factors; D004247:DNA