title: Towards evolving a better repressor.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6059, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Daber
authors.forename: Mitchell
authors.initials: M
authors.lastname: Lewis
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007763:Lac Operon / Q000235:genetics; D056968:Lac Repressors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D011487:Protein Conformation; D015202:Protein Engineering; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D056968:Lac Repressors; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D004247:DNA