Mechanisms of transcriptional activation and repression by dual plant salicylic acid receptors

Abstract For two decades, NPR1 (Nonexpressor of Pathogenesis-Related Genes 1; also called NIM1) has been known as a transcriptional activator of systemic acquired resistance in plants. NPR1 and its paralogs NPR3/NPR4 serve as dual receptors of salicylic acid (SA). Nevertheless, how NPR1 engages TGA transcription factors to recruit RNA polymerase II and initiate transcription has remained unresolved. Recent work identified Mediator complex subunit 15A (MED15A) as a bridge that couples NPR1 to the Mediator complex, and SA directly promotes NPR1–MED15A interaction, which is crucial for NPR1-mediated transcriptional activation. Meanwhile, NIM1-interacting protein 1 (NIMIN1) binds NPR3/NPR4 and the Topless (TPL) corepressors, connecting NPR3/NPR4 to Polycomb repressive complex 2 (PRC2)-mediated chromatin repression. SA disrupts the NPR3/NPR4–NIMIN1 interaction, reducing H3K27 trimethylation, increasing histone H3 acetylation at SA-responsive genes, thereby relieving NPR3/NPR4-mediated repression. These new discoveries unravel the mechanistic framework for how SA perception triggers transcriptional reprogramming and offer strategies for designing more effective SA analogs as agrochemicals to enhance crop disease resistance.