%0 Journal Article %T Genetic variation in a heat shock transcription factor modulates cold tolerance in maize. %A Gao L %A Pan L %A Shi Y %A Zeng R %A Li M %A Li Z %A Zhang X %A Zhao X %A Gong X %A Huang W %A Yang X %A Lai J %A Zuo J %A Gong Z %A Wang X %A Jin W %A Dong Z %A Yang S %J Mol Plant %V 17 %N 9 %D 2024 Sep 2 %M 39095994 %F 21.949 %R 10.1016/j.molp.2024.07.015 %X Understanding how maize (Zea mays) responds to cold stress is crucial for facilitating breeding programs of cold-tolerant varieties. Despite extensive utilization of the genome-wide association study (GWAS) approach for exploring favorable natural alleles associated with maize cold tolerance, few studies have successfully identified candidate genes that contribute to maize cold tolerance. In this study, we used a diverse panel of inbred maize lines collected from different germplasm sources to perform a GWAS on variations in the relative injured area of maize true leaves during cold stress-a trait very closely correlated with maize cold tolerance. We identified HSF21, which encodes a B-class heat shock transcription factor (HSF) that positively regulates cold tolerance at both the seedling and germination stages. Natural variations in the promoter of the cold-tolerant HSF21Hap1 allele led to increased HSF21 expression under cold stress by inhibiting binding of the basic leucine zipper bZIP68 transcription factor, a negative regulator of cold tolerance. By integrating transcriptome deep sequencing, DNA affinity purification sequencing, and targeted lipidomic analysis, we revealed the function of HSF21 in regulating lipid metabolism homeostasis to modulate cold tolerance in maize. In addition, we found that HSF21 confers maize cold tolerance without incurring yield penalties. Collectively, this study establishes HSF21 as a key regulator that enhances cold tolerance in maize, providing valuable genetic resources for breeding of cold-tolerant maize varieties.