Genome-wide gene expression is re-programmed in response to external or internal factors such as environmental stress or genetic mutation, respectively, or as a function of endogenous processes such as cell proliferation or differentiation. Here we integrate expression profiling data that have been collected by our laboratory since 2001 and that interrogate more than 900 different experimental conditions. We take advantage of this large data set to rank all genes based on their variability in gene expression across the different conditions. The most variable genes were enriched for functions such as stress response, carbohydrate metabolism and trans-membrane transport, and these genes were underrepresented for introns and tended to be close to telomeres. We then compared how overall gene regulation and variability of gene expression across conditions is affected by environmental or genetic perturbations, and by endogenous programmes. Meiotic differentiation and environmental perturbations led to substantially greater gene expression variability and overall regulation than did genetic perturbations and the transcriptional programme accompanying cell proliferation. We also used the integrated data to identify gene regulation modules using two different clustering approaches. Two major clusters, containing growth- and metabolism-related genes on one hand and stress- and differentiation-related genes on the other, were reciprocally regulated across conditions. We discuss these findings with respect to other recent reports on the regulation and evolution of gene expression.