Heterodimer Transcription Factors as Novel Gene Regulators

Synthetic bacterial communities often incorporate quorum sensing (QS) networks to enable cell-cell communication. An intrinsic component of most QS networks is dimerization of receptor proteins around QS signals. Dimers of receptors act as transcription factors, modulating gene expression in the presence of high signal concentration. For example, LuxR binds a signal, forms a homodimer, and activates an operon in a feed-forward manner that makes more signal, more receptors, and invokes bioluminescence in Vibrio fisheri. In cells with more than one type of receptor protein, homodimers and heterodimers may form. The role of heterodimers and the conditions for their formation, however, remains murky. Some authors suggest heterodimers mute genes by competitively binding QS signals or forming inactive dimers. It remains possible, however, that heterodimer formation occurs in a purposeful way. We explore the possibility that heterodimers directly regulate gene expression based on experiments with tethered dimers. From a theoretical perspective use simple thermodynamic models to examine under what conditions heterodimers might form. Using MCMC and QS receptor position weight matrices we suggest DNA binding sites may exist which favor the heterodimers over either homodimer.