Regulatory mechanisms ensuring coordinated expression of functionally related genes.

Coordinated spatiotemporal expression of large sets of genes is required for the development and homeostasis of organisms. To achieve this goal, organisms use myriad strategies where they form operons, utilize bidirectional promoters, cluster genes, share enhancers among genes by DNA looping, and form topologically associated domains and transcriptional condensates. Coexpression achieved by these different strategies is hypothesized to have functional importance in minimizing gene expression variability, establishing dosage balance to ensure stoichiometry of protein complexes, and minimizing accumulation of toxic intermediate metabolites. By combining gene-editing tools with computational modeling, recent studies tested the advantages of adjacent genes located in pairs and clusters. We propose that with the advancement of gene editing, single-cell sequencing, and imaging tools, one could readily test the functional importance of different coexpression strategies in a variety of biological processes.