Mechanistic understanding of the role of two Nudix proteins in plant immunity

Plants use intricate signaling networks to fine-tune defense pathways in response to attack by different pathogens, leading to broad transcriptional reprogramming. Epigenetic mechanism/chromatin remodeling plays a vital role in regulating expression of defense-related genes; however, the mechanism that control epigenetic modifications associated with defense pathway genes is largely unknown.

Nudix proteins, found in all classes of organisms, have diverse substrates but most of them hydrolyze nucleoside diphosphate derivatives. We previously identified two Arabidopsis Nudix proteins, NUDT6 and NUDT7, as negative regulators of the immune response. Our recent findings raise an intriguing possibility that NUDT6 and NUDT7 might function in epigenetic control of the defense pathway to prevent unnecessary or excessive activation of defense mechanism. We and another group have identified two histone acetyltransferases (HAT), HAC5 and GCN5, as putative NUDT7- and NUDT6- interating proteins, respectively. We recently found that the loss-of-function mutations of NUDT6 and NUDT7 make the plants hypersensitive to epigenetic modifications. Many epigenetic suppressors of the nudt6 nudt7 double mutant have been obtained.

In this proposal, we will validate the interactions of NUDT7-HAC5 and NUDT6-GCN5. We will examine whether NUDT6 and NUDT7 modulate HAC5 and GCN5 function by hydrolyzing acetyl-CoA, a nucleotide derivative and the acetyl donor in the HAT- catalyzed histone acetylation reaction. Histone acetylation and DNA methylation patterns will be analyzed and compared between wildtype, the nudt mutants, and epigenetic suppressors of the nudt6 nudt7 mutant to reveal the effects of the mutations on epigenetic modifications linked to the defense pathway genes and transgenerational memory of acquired resistance. Besides, genetic analysis will be performed to identify other components in the NUDT6/NUDT7-mediated defense pathway. The proposed study could make a significant contribution toward unraveling the control mechanism of plant immunity.