Interplay between gene expression noise and regulatory network architecture

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• 作者：Guilhem Chalancon¹ ; ^{guilhem@mrc-lmb.cam.ac.uk} ; Charles N.J. Ravarani¹ ; S. Balaji² ; Alfonso Martinez-Arias³ ; L. Aravind⁴ ; Raja Jothi⁵ ; M. Madan Babu¹ ; ^{madanm@mrc-lmb.cam.ac.uk}
• 关键词：expression noise ; gene regulatory network ; persistence ; phenotypic variation ; single-cell analysis ; differentiation ; development
• 刊名：Trends in Genetics
• 出版年：2012
• 期刊代码：256_01689525
• 类别：med
• 出版时间：May, 2012
• 卷：28
• 期：5
• 页码：221-232
• 文件大小：3154 K

摘要

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.