Molecular regulation of hypoxia responses by H3K4me3 histone demethylases in Arabidopsis thaliana

Climate change is increasing precipitation and flooding in many regions, causing major crop losses due to low oxygen (hypoxia) in waterlogged plants. Plant hypoxia responses are known to be regulated through the N-degron pathway, which targets transcriptional regulators for degradation in the presence of oxygen. However, our transcriptomic analyses of Arabidopsis thaliana N-degron pathway mutant seedlings show upregulation of only ∼45% of core hypoxia response genes, indicating that additional regulatory mechanisms are involved. In mammals, histone demethylases contribute to hypoxia responses due to their oxygen-dependent activity. Whether histone demethylases regulate plant hypoxia responses has remained unclear. Histone H3 lysine 4 tri-methylation (H3K4me3) promotes gene activation and is removed in plants by demethylases such as JUMONJI14 (JMJ14), JMJ16, and JMJ17. Here, we show that global H3K4me3 levels rise in wild-type A. thaliana seedlings exposed to hypoxia. In N-degron mutants, elevated H3K4me3 correlates with activation of hypoxia-responsive genes. We dissected the transcriptomic response to hypoxia and found enrichment of hypoxia response genes and stronger induction of certain core hypoxia response genes in jmj14/16/17 compared to wild-type seedlings. These data indicate a novel role for H3K4 histone demethylases in regulating molecular hypoxia responses in plants, thereby unfolding new areas for exploration.