Stress-responsive transcription factor families are key components of the core abiotic stress response in maize.

Abiotic stresses, including drought, salt, heat, cold, flooding, and low nitrogen, have devastating impacts on agriculture and are increasing in frequency globally due to climate change. Plants can experience multiple abiotic stresses simultaneously or sequentially within a single growing season, and combinatorial stresses elicit shared or overlapping molecular and physiological responses. Here, we searched for core stress responsive genes in maize across diverse abiotic stressors through meta-analysis of public RNAseq data. Our analysis revealed significant heterogeneity in gene expression across datasets due to factors such as tissue type, genotype, and experimental conditions, which we mitigated through batch correction. Using nearly 1,900 RNAseq samples with both traditional set operations and a novel random forest machine learning approach, we identified a core set of 744 stress-responsive genes across the six stresses. These core genes are enriched in transcription factors, including stress-responsive families such as AP2/ERF-ERF, NAC, bZIP, HSF, and C2C2-CO-like. Co-expression network analysis demonstrated that these core TFs are co-expressed with stress-specific peripheral genes, supporting their role in regulating both generalized and stress-specific responses. Our results suggest that maize employs a conserved yet flexible transcriptional strategy to respond to abiotic stresses, with core TFs acting as potential regulators of both universal and stress-specific pathways. These findings provide a valuable resource for understanding stress tolerance mechanisms and for guiding future breeding and engineering efforts to enhance maize resilience under climate change.