Bioinformatics Advance Access originally published online on May 13, 2009
Bioinformatics 2009 25(15):1898-1904; doi:10.1093/bioinformatics/btp316
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Hub genes with positive feedbacks function as master switches in developmental gene regulatory networks
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Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea
* To whom correspondence should be addressed.
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Abstract |
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Motivation: Spatio-temporal regulation of gene expression is an indispensable characteristic in the development processes of all animals. ‘Master switches’, a central set of regulatory genes whose states (on/off or activated/deactivated) determine specific developmental fate or cell-fate specification, play a pivotal role for whole developmental processes. In this study on genome-wide integrative network analysis the underlying design principles of developmental gene regulatory networks are examined.
Results: We have found an intriguing design principle of developmental networks: hub nodes, genes with high connectivity, equipped with positive feedback loops are prone to function as master switches. This raises the important question of why the positive feedback loops are frequently found in these contexts. The master switches with positive feedback make the developmental signals more decisive and robust such that the overall developmental processes become more stable. This finding provides a new evolutionary insight: developmental networks might have been gradually evolved such that the master switches generate digital-like bistable signals by adopting neighboring positive feedback loops. We therefore propose that the combined presence of positive feedback loops and hub genes in regulatory networks can be used to predict plausible master switches.
Contact: ckh{at}kaist.ac.kr
Supplementary information: Supplementary data are available at Bioinformatics online.
The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.
Present address: Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo 113-8685, Japan.
Associate Editor: Limsoon Wong
Received on December 11, 2008; revised on May 11, 2009; accepted on May 11, 2009
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