MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK.
Trends Genet. 2012 May;28(5):221-32. doi: 10.1016/j.tig.2012.01.006. Epub 2012 Feb 25.
Complex regulatory networks orchestrate most cellular processes in biological systems. Genes in such networks are subject to expression noise, resulting in isogenic cell populations exhibiting cell-to-cell variation in protein levels. Increasing evidence suggests that cells have evolved regulatory strategies to limit, tolerate or amplify expression noise. In this context, fundamental questions arise: how can the architecture of gene regulatory networks generate, make use of or be constrained by expression noise? Here, we discuss the interplay between expression noise and gene regulatory network at different levels of organization, ranging from a single regulatory interaction to entire regulatory networks. We then consider how this interplay impacts a variety of phenomena, such as pathogenicity, disease, adaptation to changing environments, differential cell-fate outcome and incomplete or partial penetrance effects. Finally, we highlight recent technological developments that permit measurements at the single-cell level, and discuss directions for future research.
复杂的调控网络协调着生物系统中大多数的细胞过程。在这些网络中的基因受到表达噪声的影响，导致同基因的细胞群体在蛋白质水平上表现出细胞间的变异。越来越多的证据表明，细胞已经进化出调控策略来限制、容忍或放大表达噪声。在这种情况下，出现了一些基本问题：基因调控网络的结构如何产生、利用或受表达噪声的限制？在这里，我们讨论了表达噪声与基因调控网络在不同组织层次之间的相互作用，从单个调控相互作用到整个调控网络。然后，我们考虑这种相互作用如何影响各种现象，如致病性、疾病、对环境变化的适应、不同的细胞命运结果以及不完全或部分外显效应。最后，我们强调了最近允许在单细胞水平进行测量的技术发展，并讨论了未来研究的方向。
