Gene

Cell biology

Biology

Enhancer

Gene cluster

Expression (computer science)

Operon

Regulation of gene expression

Computer science

Computational biology

Genetics

Regulatory sequence

Escherichia coli

Programming language

Gene expression

Trends in Genetics

HighlightsDuring development and homeostasis, organisms use diverse strategies such as operons, gene clusters, topological associated domains, and transcriptional condensates to coordinate spatiotemporal expression of large sets of genes.With recent development in gene-editing tools and computational modeling, recent studies have revealed the advantages of adjacently locating genes in pairs and clusters.Single-cell imaging and high-throughput methods will elucidate the hierarchy among different strategies to achieve coordinated gene expression.Organizing genes in pairs and clusters, while providing some benefits, might also increase mutational burdens where a single mutation could influence expression of multiple neighboring genes.AbstractCoordinated 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.

Regulatory mechanisms ensuring coordinated expression of functionally related genes