Aurell Erik, d'Hérouël Aymeric Fouquier, Malmnäs Claes, Vergassola Massimo
Department of Computational Biology, KTH-Royal Institute of Technology, AlbaNova University Center, Stockholm, Sweden.
Phys Biol. 2007 Jun 22;4(2):134-43. doi: 10.1088/1478-3975/4/2/006.
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.
转录调控在很大程度上受转录因子与DNA结合的概况及动力学的支配。随机效应是这种动力学所固有的，并且对于生物体能够引发特定的细胞反应而言，与功能位点的结合必须以一定的特异性进行控制。特异性源于转录因子蛋白的结合亲和力与细胞丰度之间的相互作用，因此这类蛋白与DNA的结合受其化学势的控制。我们将芽殖酵母中的大规模蛋白质丰度数据与所有具有已知DNA结合位点序列的转录因子的结合亲和力相结合，以评估它们在指数生长期的化学势行为。相当一部分转录因子显然非特异性地与DNA结合，并且观察到的丰度仅勉强足以确保功能位点的高占有率。我们认为这一特征的生物学原因与其噪声过滤结果有关：低于生理水平的丰度不会导致功能靶点的显著结合，因此可能会抑制受调控基因的错误表达。
