Smoking out the masters: Transcriptional regulators for nicotine biosynthesis in tobacco

Nicotine and tropane alkaloids are specialized metabolites produced in certain species of Solanaceae, and some of these alkaloids have been used as pharmacological agents. In tobacco plants, nicotine is a defensive toxin against herbivorous insects, and jasmonate (JA) signaling leads to the induction of nicotine biosynthesis. JA-responsive structural genes of the nicotine pathway have been identified as being down-regulated in a low-nicotine tobacco mutant, which possesses mutant alleles at two loci, NICOTINE1 and NICOTINE2 (NIC1 and NIC2). A group of JA-responsive genes that encode homologous ERF transcription factors are clustered at the NIC2 locus and deleted in the mutant. These NIC2-locus ERFs up-regulate the structural genes of the biosynthetic pathway by recognizing GCC-like boxes in their promoters, forming a regulon for nicotine biosynthesis with the downstream targeted genes. The three basic components in JA signaling, COI1, JAZ, and MYC2, are required for JA-induced nicotine formation in tobacco. The bHLH transcription factor MYC2 positively regulates the structural genes, both directly by recognizing G boxes in their promoters and indirectly by up-regulating NIC2-locus ERF genes. Molecular elucidation of nicotine regulation would lead us to better understand the JA-dependent regulation of a wide range of phytochemicals.