Thermodynamic models predict quantitative expression levels driven by synthetic cis-regulatory modules in the Drosophila embryo. Daniel K. Bork^1,2, Adam S. Brown², Lily Li², Robert A. Drewell², Jacqueline M. Dresch¹. 1) Mathematics Department, Harvey Mudd College, Claremont, CA; 2) Biology Department, Harvey Mudd College, Claremont, CA.

   Quantitative models of gene expression offer valuable insight into the molecular basis for activation and short-range repression in eukaryotic organisms. High-throughput sequencing and transcriptomics elucidate the sequence-level nature of specific transcription factor binding sites in the Drosophila embryo. Thermodynamic models can be used to predict quantitative levels of gene expression given the DNA sequence and concentration gradients of the TFs involved in regulation.
   Thermodynamic models can also be fit to quantitative expression data obtained from in situ hybridization of synthetic reporter genes under the control of cis-regulatory modules, and begin to uncover the nature of TF-induced regulation of gene expression. The use of synthetic constructs with a small number of binding sites decreases the complexity of TF interactions, thus increasing parameter identifiability and model reproducibility. For this reason, we have applied thermodynamic models of gene regulation to synthetic cis-regulatory modules designed to investigate the binding strength of specific TFs and the role of certain TF interactions, such as quenching and competition, on short-range repression during early Drosophila development.