Cis-regulatory information determines where, when, and how much of a gene is transcribed. Because of the complexity of eukaryotic promoters, generally the questions of when and where are asked. These can be answered fairly well using simple Boolean logic and a knowledge of the presence or absence of a transcription factor binding site in individual promoters, and when and where that factor is expressed. As we improve our understanding of the binding kinetics of these factors though, we can begin to answer the more difficult question of how much. Bacterial promoters are orders less complicated than eukaryotic promoters, but are still composed of multiple cooperatively acting factors. If we can determine how the regulatory information of multiple binding components is integrated to determine transcriptional output in bacteria, we can then begin to apply these principles to more complicated promoters. I have developed an information theory based model to describe the binding of the multi-meric transcriptional initiation complex in E. coli. I am now testing assumptions made by this model about how individual promoter components contribute to the overall initiation complex stability and ultimately transcriptional output.
I am also interesting in the evolution of transcription factor binding domains. New transcriptional control systems could have evolved in the cell through duplication of an existing transcription factor gene and then subsequent mutations of the duplication. I am interested in understanding how plastic the binding domain for a given transcription factor is, and how easily it can be shifted to a unique separable recognizer. To do this, I select for variants of the E. coli transcription factor MarA against different sequences at different affinity requirements, and measure their binding to a large number of DNA sequences.
Eisen Lab Publications: