Interplay between gene expression noise and regulatory network architecture

被引:189
作者
Chalancon, Guilhem [1 ]
Ravarani, Charles N. J. [1 ]
Balaji, S. [2 ,3 ,4 ]
Martinez-Arias, Alfonso [5 ]
Aravind, L. [6 ]
Jothi, Raja [7 ]
Babu, M. Madan [1 ]
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England
[2] Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[5] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England
[6] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA
[7] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA
基金
英国医学研究理事会; 欧洲研究理事会;
关键词
expression noise; gene regulatory network; persistence; phenotypic variation; single-cell analysis; differentiation; development; DETERMINES CELL FATE; GENOMIC ANALYSIS; VARIABILITY; EVOLUTION; DYNAMICS; SELECTION; PROTEIN; STOCHASTICITY; ORGANIZATION; PROPAGATION;
D O I
10.1016/j.tig.2012.01.006
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
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.
引用
收藏
页码:221 / 232
页数:12
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