Nitrate fertilizers exacerbate Fe deficiency in plants, a phenomenon traditionally attributed to rhizosphere alkalinization that reduces Fe bioavailability. However, whether nitrate itself acts as a signaling molecule in this process has remained unclear. Here, we demonstrate that nitrate functions as an essential signaling molecule that regulates Fe deficiency responses in Arabidopsis through NLP7, a central nitrate sensor. Nitrate deficiency, but not ammonium deficiency, abolishes Fe deficiency-induced chlorosis and suppresses the expression of Fe uptake genes (IRT1, FIT), confirming nitrate's specific signaling role. We show that Fe deficiency triggers rapid nuclear accumulation of NLP7 in a strictly nitrate-dependent manner. Loss-of-function nlp7 mutants exhibit attenuated Fe deficiency responses, including reduced FCR activity and diminished induction of IRT1, FRO2, and FIT, yet exhibit reduced chlorosis under Fe deficiency, indicating alleviation of stress symptoms rather than genuine enhancement of Fe tolerance. Transcriptome and molecular analyses identify NIGT1.3 as a direct transcriptional target of NLP7; NIGT1.3 in turn represses NRT1.1 transcription, establishing a regulatory cascade from nitrate sensing to Fe homeostasis modulation. Notably, growth-chlorophyll correlation analysis reveals that plant growth positively correlates with chlorophyll content under Fe sufficiency but negatively correlates under Fe deficiency, uncovering a growth-stress trade-off mediated by the NLP7-NIGT1.3 module. Collectively, our findings establish NLP7 as a central hub integrating nitrate signaling with Fe deficiency responses and reveal a regulatory mechanism that balances stress adaptation with growth maintenance under combined nitrate and Fe nutritional stress.

Iron (Fe) deficiency is a major abiotic stress limiting crop production. HDC1, a component of the histone deacetylase complex, plays important roles in plant development and stress responses, yet its function in Fe deficiency responses remains unclear. This study reveals that HDC1 promotes the reallocation and utilization of cell wall pectin-bound Fe under Fe-limited conditions through an ATAF1-dependent epigenetic pathway regulating the expression of the cell wall–associated receptor kinase WAK1. We found that Fe deficiency triggers HDC1 protein degradation via the ubiquitin-proteasome pathway, leading to increased acetylation of histone H3 at Lysines 9 and 14 (H3K9ac/H3K14ac). RNA sequencing and chromatin immunoprecipitation-quantitative PCR analyses identified WAK1 as a key downstream gene negatively regulated by HDC1. Mechanistically, the transcription factor ATAF1 directly binds to and activates the WAK1 promoter, while HDC1 represses WAK1 transcription by indirectly promoting ATAF1 ubiquitination and degradation. Loss of WAK1 function results in increased pectin content, enhanced Fe sequestration in the cell wall, and heightened sensitivity to Fe deficiency. Conversely, the hdc1 mutant exhibits upregulated WAK1 expression, reduced pectin content, enhanced release of apoplastic Fe, and increased Fe translocation to shoots, collectively improving Fe deficiency tolerance. Together, our findings uncover an HDC1-ATAF1-WAK1 signaling module and elucidate an epigenetic mechanism wherein histone deacetylation regulates cell wall metabolism to promote Fe reutilization, providing new theoretical insights for improving plant Fe nutrition efficiency.

Nitrogen is a necessary macronutrient that limits plant growth and crop productivity, yet excessive fertilizer application has resulted in serious environmental consequences. The NIN-like protein (NLP) family consists of plant-specific transcription factors that serve as central regulators of nitrate signaling. In 2022, the discovery of NLP7 as an intracellular nitrate receptor represented a major conceptual shift from transcriptional regulation to signal perception. This review systematically summarizes the molecular architecture of NLP proteins, focusing on the conserved RWP-RK DNA-binding domain, the PB1 protein-protein interaction module, and the GAF-like domain associated with the integration of multiple signals. It also examines the species-specific expansion and evolutionary diversification of the NLP family, as well as the multilayered mechanisms that regulate NLP activity, including phosphorylation as a signal-dependent molecular switch, SUMOylation as a negative feedback mechanism, transcriptional regulation of downstream targets, and PB1-mediated protein interaction networks. In addition to nitrate signaling, NLPs serve as central hubs linking nitrogen and carbon metabolism and mediating responses to abiotic stresses including cold, heat, salinity, and iron deficiency. Notably, the NLP7–NIGT1.3 module coordinates a growth–stress trade-off during iron deficiency by modulating nitrate signaling intensity, revealing a previously unrecognized mechanism for balancing stress adaptation with growth maintenance. NLPs also participate in developmental processes, including lateral root formation and symbiotic nodulation. Finally, this review highlights the potential of NLP-based approaches for crop genetic improvement, such as overexpression of key NLP genes or CRISPR/Cas-mediated editing, to improve nitrogen use efficiency, stress tolerance, and yield. Collectively, these insights provide a theoretical foundation for developing crop varieties with improved nitrogen-use efficiency and context-dependent stress adaptation, while acknowledging the inherent trade-offs between productivity and resilience.