Ramsey Stephen A, Smith Jennifer J, Orrell David, Marelli Marcello, Petersen Timothy W, de Atauri Pedro, Bolouri Hamid, Aitchison John D
Institute for Systems Biology, 1441 N 34th Street, Seattle, Washington 98103, USA.
Nat Genet. 2006 Sep;38(9):1082-7. doi: 10.1038/ng1869. Epub 2006 Aug 27.
Transcriptional noise is known to be an important cause of cellular heterogeneity and phenotypic variation. The extent to which molecular interaction networks may have evolved to either filter or exploit transcriptional noise is a much debated question. The yeast genetic network regulating galactose metabolism involves two proteins, Gal3p and Gal80p, that feed back positively and negatively, respectively, on GAL gene expression. Using kinetic modeling and experimental validation, we demonstrate that these feedback interactions together are important for (i) controlling the cell-to-cell variability of GAL gene expression and (ii) ensuring that cells rapidly switch to an induced state for galactose uptake.
转录噪声是细胞异质性和表型变异的一个重要原因。分子相互作用网络在多大程度上可能已经进化到可以过滤或利用转录噪声，这是一个备受争议的问题。调节半乳糖代谢的酵母遗传网络涉及两种蛋白质，Gal3p和Gal80p，它们分别对GAL基因表达进行正反馈和负反馈。通过动力学建模和实验验证，我们证明这些反馈相互作用共同对于（i）控制GAL基因表达的细胞间变异性以及（ii）确保细胞迅速切换到诱导状态以摄取半乳糖很重要。
