A General Mechanism for Network-Dosage Compensation in Gene Circuits

被引：74

作者：

Acar, Murat ^{[1
]}

Pando, Bernardo F. ^{[2
]}

Arnold, Frances H. ^{[3
,4
]}

Elowitz, Michael B. ^{[1
,5
,6
]}

van Oudenaarden, Alexander ^{[2
,7
]}

机构：

[1] CALTECH, Div Biol, Pasadena, CA 91125 USA

[2] MIT, Dept Phys, Cambridge, MA 02139 USA

[3] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA

[4] CALTECH, Div Biochem & Mol Biophys, Pasadena, CA 91125 USA

[5] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA

[6] CALTECH, Dept Appl Phys, Pasadena, CA 91125 USA

[7] MIT, Dept Biol, Cambridge, MA 02139 USA

来源：

SCIENCE | 2010年 / 329卷 / 5999期

关键词：

SACCHAROMYCES-CEREVISIAE; BINDING; YEAST; ROBUSTNESS; PROTEIN; REPRESSION; SYSTEMS; GAL80P; MEMORY; SIGNAL;

D O I：

10.1126/science.1190544

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Coping with variations in network dosage is crucial for maintaining optimal function in gene networks. We explored how network structure facilitates network-level dosage compensation. By using the yeast galactose network as a model, we combinatorially deleted one of the two copies of its four regulatory genes and found that network activity was robust to the change in network dosage. A mathematical analysis revealed that a two-component genetic circuit with elements of opposite regulatory activity (activator and inhibitor) constitutes a minimal requirement for network-dosage invariance. Specific interaction topologies and a one-to-one interaction stoichiometry between the activating and inhibiting agents were additional essential elements facilitating dosage invariance. This mechanism of network-dosage invariance could represent a general design for gene network structure in cells.

引用

页码：1656 / 1660

页数：6

共 28 条

[1] Enhancement of cellular memory by reducing stochastic transitions [J].