Title: Computational Models of Kruppel Enhancers Suggest Trade-Offs in Transcriptional Noise and Fidelity
Abstract:
Shadow enhancers are short regions of DNA that regulate developmental genes and ensure consistent expression patterns within the embryo. These multi-enhancer systems have been observed to drive more robust transcription than single enhancer systems. Nevertheless, it remains unclear why the arrangement of transcription factor (TF) binding sites happens across multiple enhancers rather than within a single large enhancer. In this work, we use a mathematical and computational approach to study enhancer systems with varying numbers of TF binding sites, enhancers, and distinct binding affinities. We model these systems as chemical reaction networks under stochastic dynamics and analyze the resulting trends in transcriptional noise and fidelity. The results of this work suggest that there may not be a strong selection pressure at the transcriptional level on having multiple enhancers. We also compare strategies for enhancer origins and present modeling results for the duplication and splitting of enhancers.
Shadow enhancers are short regions of DNA that regulate developmental genes and ensure consistent expression patterns within the embryo. These multi-enhancer systems have been observed to drive more robust transcription than single enhancer systems. Nevertheless, it remains unclear why the arrangement of transcription factor (TF) binding sites happens across multiple enhancers rather than within a single large enhancer. In this work, we use a mathematical and computational approach to study enhancer systems with varying numbers of TF binding sites, enhancers, and distinct binding affinities. We model these systems as chemical reaction networks under stochastic dynamics and analyze the resulting trends in transcriptional noise and fidelity. The results of this work suggest that there may not be a strong selection pressure at the transcriptional level on having multiple enhancers. We also compare strategies for enhancer origins and present modeling results for the duplication and splitting of enhancers.