ERF Gene Clusters: Working Together to Regulate Metabolism

Plants produce structurally diverse specialized metabolites, including bioactive alkaloids and terpenoids, in response to biotic and abiotic environmental stresses. The APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) family of transcription factors (TFs) play key roles in regulating biosynthesis of specialized metabolites. Increasing genomic and functional evidence shows that a subset of the ERF genes occurs in clusters on the chromosomes. These jasmonate-responsive ERF TF gene clusters control the biosynthesis of many important metabolites, from natural products, such as nicotine and steroidal glycoalkaloids (SGAs), to pharmaceuticals, such as artemisinin, vinblastine, and vincristine. Here, we review the function, regulation, and evolution of ERF clusters and highlight recent advances in understanding the distinct roles of clustered ERF genes and their possible application in metabolic engineering.