Abstract
Cells regulate expression their genome by means of a diverse repertoire of molecular mechanisms. However, little is known about their design principles or how these are influenced by underlying physical constraints. An early theory of gene regulation for inducible systems predicted that expression of the regulator and regulated proteins would be perfectly coupled (coordinate expression of regulator) when the regulator is a repressor and completely uncoupled (invariant expression of regulator) when the regulator is an activator. The experimental data then available tended to support these predictions, but there were notable exceptions. Here, we describe an extended theory, which takes into account the subunit structure of regulator proteins. The number of subunits determines the allowable range of values for the regulatory parameters, and, as a consequence, new rules for the prediction of gene circuitry emerge. The theory predicts perfectly coupled circuits with repressors, but only when the capacity for induction is "small"; it predicts completely uncoupled circuits with repressors when the capacity is "large". This theory also predicts completely uncoupled circuits with activators when the capacity for induction is small; it predicts perfectly coupled circuits with activators when the capacity is large. These new predictions are more fully in accord with available experimental evidence.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 739-755 |
| Number of pages | 17 |
| Journal | Journal of Molecular Biology |
| Volume | 248 |
| Issue number | 4 |
| DOIs | |
| State | Published - May 12 1995 |
| Externally published | Yes |
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Keywords
- design principles
- gene circuits
- inducible genes
- regulation
- regulator proteins
ASJC Scopus subject areas
- Molecular Biology
- Virology
Cite this
Subunit Structure of Regulator Proteins Influences the Design of Gene Circuitry : Analysis of Perfectly Coupled and Completely Uncoupled Circuits. / Hlavacek, William S.; Savageau, Michael A.
In: Journal of Molecular Biology, Vol. 248, No. 4, 12.05.1995, p. 739-755.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Subunit Structure of Regulator Proteins Influences the Design of Gene Circuitry
T2 - Analysis of Perfectly Coupled and Completely Uncoupled Circuits
AU - Hlavacek, William S.
AU - Savageau, Michael A.
PY - 1995/5/12
Y1 - 1995/5/12
N2 - Cells regulate expression their genome by means of a diverse repertoire of molecular mechanisms. However, little is known about their design principles or how these are influenced by underlying physical constraints. An early theory of gene regulation for inducible systems predicted that expression of the regulator and regulated proteins would be perfectly coupled (coordinate expression of regulator) when the regulator is a repressor and completely uncoupled (invariant expression of regulator) when the regulator is an activator. The experimental data then available tended to support these predictions, but there were notable exceptions. Here, we describe an extended theory, which takes into account the subunit structure of regulator proteins. The number of subunits determines the allowable range of values for the regulatory parameters, and, as a consequence, new rules for the prediction of gene circuitry emerge. The theory predicts perfectly coupled circuits with repressors, but only when the capacity for induction is "small"; it predicts completely uncoupled circuits with repressors when the capacity is "large". This theory also predicts completely uncoupled circuits with activators when the capacity for induction is small; it predicts perfectly coupled circuits with activators when the capacity is large. These new predictions are more fully in accord with available experimental evidence.
AB - Cells regulate expression their genome by means of a diverse repertoire of molecular mechanisms. However, little is known about their design principles or how these are influenced by underlying physical constraints. An early theory of gene regulation for inducible systems predicted that expression of the regulator and regulated proteins would be perfectly coupled (coordinate expression of regulator) when the regulator is a repressor and completely uncoupled (invariant expression of regulator) when the regulator is an activator. The experimental data then available tended to support these predictions, but there were notable exceptions. Here, we describe an extended theory, which takes into account the subunit structure of regulator proteins. The number of subunits determines the allowable range of values for the regulatory parameters, and, as a consequence, new rules for the prediction of gene circuitry emerge. The theory predicts perfectly coupled circuits with repressors, but only when the capacity for induction is "small"; it predicts completely uncoupled circuits with repressors when the capacity is "large". This theory also predicts completely uncoupled circuits with activators when the capacity for induction is small; it predicts perfectly coupled circuits with activators when the capacity is large. These new predictions are more fully in accord with available experimental evidence.
KW - design principles
KW - gene circuits
KW - inducible genes
KW - regulation
KW - regulator proteins
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UR - http://www.scopus.com/inward/citedby.url?scp=0029033413&partnerID=8YFLogxK
U2 - 10.1006/jmbi.1995.0257
DO - 10.1006/jmbi.1995.0257
M3 - Article
C2 - 7752237
AN - SCOPUS:0029033413
VL - 248
SP - 739
EP - 755
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 4
ER -