Hysteresis in a synthetic mammalian gene network

AUTOR(ES)

Kramer, Beat P.

FONTE

National Academy of Sciences

RESUMO

Bistable and hysteretic switches, enabling cells to adopt multiple internal expression states in response to a single external input signal, have a pivotal impact on biological systems, ranging from cell-fate decisions to cell-cycle control. We have designed a synthetic hysteretic mammalian transcription network. A positive feedback loop, consisting of a transgene and transactivator (TA) cotranscribed by TA's cognate promoter, is repressed by constitutive expression of a macrolide-dependent transcriptional silencer, whose activity is modulated by the macrolide antibiotic erythromycin. The antibiotic concentration, at which a quasi-discontinuous switch of transgene expression occurs, depends on the history of the synthetic transcription circuitry. If the network components are imbalanced, a graded rather than a quasi-discontinuous signal integration takes place. These findings are consistent with a mathematical model. Synthetic gene networks, which are able to emulate natural gene expression behavior, may foster progress in future gene therapy and tissue engineering initiatives.

Documentos Relacionados

• A gene network model accounting for development and evolution of mammalian teeth
• CLONAL GROWTH OF MAMMALIAN CELLS IN A CHEMICALLY DEFINED, SYNTHETIC MEDIUM*
• A Purkinje Conduction Network in the Myocardium of the Mammalian Ventricles1
• Structure and function in rhodopsin: high level expression of a synthetic bovine opsin gene and its mutants in stable mammalian cell lines.
• The mammalian mitogen activated protein kinase network