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PEDS Advance Access originally published online on September 2, 2009
Protein Engineering Design and Selection 2009 22(11):673-683; doi:10.1093/protein/gzp051
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Towards evolving a better repressor

Robert Daber and Mitchell Lewis1

Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 37th and Hamilton Walk, Philadelphia, PA 19104-6059, USA

1 To whom correspondence should be addressed. E-mail: lewis{at}mail.med.upenn.edu

Transcriptional regulation is an essential component of all metabolic pathways. At the most basic level, a protein binds to a particular DNA sequence (operator) on the genome and either positively or negatively alters the level of transcription. Together, the protein and its operator form an epigenetic switch that regulates gene expression. In an effort to produce a ‘better’ switch, we have discovered novel facets of the lac operon that are responsible for optimal functionality. We have uncovered a relationship between operator binding affinity and inducibility and demonstrated that the operator DNA is not a passive component of a genetic switch; it is responsible for establishing binding affinity, specificity as well as translational efficiency. In addition, an operator's directionality can indirectly affect gene expression. Unraveling the basic properties of this classical epigenetic switch demonstrates that multiple factors must be optimized in designing a better switch.

Keywords: induction/regulation/repression/transcription

Received June 10, 2009; revised July 27, 2009; accepted July 27, 2009.


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