Asymmetric positive feedback loops reliably control biological responses.
Mol Syst Biol
; 8: 577, 2012 Apr 24.
Article
em En
| MEDLINE
| ID: mdl-22531117
ABSTRACT
Positive feedback is a common mechanism enabling biological systems to respond to stimuli in a switch-like manner. Such systems are often characterized by the requisite formation of a heterodimer where only one of the pair is subject to feedback. This ASymmetric Self-UpREgulation (ASSURE) motif is central to many biological systems, including cholesterol homeostasis (LXRα/RXRα), adipocyte differentiation (PPARγ/RXRα), development and differentiation (RAR/RXR), myogenesis (MyoD/E12) and cellular antiviral defense (IRF3/IRF7). To understand why this motif is so prevalent, we examined its properties in an evolutionarily conserved transcriptional regulatory network in yeast (Oaf1p/Pip2p). We demonstrate that the asymmetry in positive feedback confers a competitive advantage and allows the system to robustly increase its responsiveness while precisely tuning the response to a consistent level in the presence of varying stimuli. This study reveals evolutionary advantages for the ASSURE motif, and mechanisms for control, that are relevant to pharmacologic intervention and synthetic biology applications.
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Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Modelos Moleculares
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Regulação Fúngica da Expressão Gênica
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Retroalimentação Fisiológica
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Biologia de Sistemas
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article