Herbicide Metabolic Resistance in Poaceae Plants via the GA-GID1/DELLA-DOF2-P450s Module

Barnyard grass (Echinochloa crus-galli) is one of the world's most important weeds, and the evolution of herbicide resistance in this species threatens rice and maize production. Cytochrome P450-mediated metabolic herbicide detoxification is a prevalent resistance mechanism, yet its upstream regulatory control has remained elusive. This study uncovers an important regulatory module linking gibberellin (GA) signaling to herbicide detoxification. We identify the DOF-family transcription factor DOF2 as an important regulator that directly activates herbicide detoxification genes, including CYP81A21 and CYP704A371 in E. crus-galli, and CYP81A6 in rice. DOF2 is constitutively elevated in resistant E. crus-galli and further induced by herbicide treatment. Overexpression of DOF2 in E. crus-galli or its ortholog in rice confers resistance, while knockout of the rice ortholog increases susceptibility. Mechanistically, the DELLA protein SLR1 interacts with DOF2 to repress its transcriptional activity, and GA signaling relieves this repression. We further show that herbicide treatment rapidly upregulates GA biosynthesis genes, leading to increased GA levels that trigger this pathway. Importantly, this GA-GID1/DELLA-DOF2-P450 axis operates in at least two Poaceae species, suggesting a conserved regulatory logic. These findings establish a direct mechanistic link between phytohormone signaling and metabolic herbicide resistance, with implications for weed resistance management and crop tolerance improvement.