Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Dosage Compensation, Genetic*
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Feedback, Physiological
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Galactose / metabolism*
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Gene Expression Regulation, Fungal
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Gene Regulatory Networks*
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Genes, Fungal
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Genes, Regulator
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Models, Genetic
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Monosaccharide Transport Proteins / genetics*
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Monosaccharide Transport Proteins / metabolism
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Protein Binding
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / genetics*
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Saccharomyces cerevisiae Proteins / metabolism
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Signal Transduction / genetics
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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GAL2 protein, S cerevisiae
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GAL4 protein, S cerevisiae
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GAL80 protein, S cerevisiae
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Gal3 protein, S cerevisiae
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Monosaccharide Transport Proteins
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Galactose