Over the past two decades, numerous studies have been conducted with the aim of identifying the structures within regulatory networks responsible for gene expression patterns. Gene expression plasticity for instance has been associated with many network structures, but both theoretical results and empirical observations were often equivocal. Our objective was to decipher the regulatory causes of gene expression plasticity, with a particular focus on identifying the relevant structures in regulatory networks that might influence the sensitivity to environmental factors. We sought the common regulatory structures associated with gene expression plasticity between predictions from an evolutionary simulation model and the global regulatory network from Escherichia coli . Congruent results from empirical and theoretical approaches confirmed that selection promotes more regulation towards plastic genes and, as a consequence, plastic genes were more often regulated by feedforward loops than non-plastic genes. Selection tends to bias the distribution of regulatory loop motifs towards positive feedforward and diamond loops, but this enrichment in specific structures was the same in plastic and non-plastic genes. The inability to predict gene expression plasticity from the network regulatory structure opens new questions about the nature of the missing information in current systems biology databases and the evolutionary causes of gene expression plasticity.