Primed to persevere: Hypoxia regulation from epigenome to protein accumulation in plants.

Plant cells regularly encounter hypoxia (low-oxygen conditions) as part of normal growth and development, or in response to environmental stresses such as flooding. In recent years, our understanding of the multi-layered control of hypoxia-responsive gene expression has greatly increased. In this Update, we take a broad look at the epigenetic, transcriptional, translational, and post-translational mechanisms that regulate responses to low-oxygen levels. We highlight how a network of post-translational modifications (including phosphorylation), secondary messengers, transcriptional cascades, and retrograde signals from the mitochondria and endoplasmic reticulum (ER) feed into the control of transcription factor activity and hypoxia-responsive gene transcription. We discuss epigenetic mechanisms regulating the response to reduced oxygen availability, through focussing on active and repressive chromatin modifications and DNA methylation. We also describe current knowledge of the co- and post-transcriptional mechanisms that tightly regulate mRNA translation to coordinate effective gene expression under hypoxia. Finally, we present a series of outstanding questions in the field and consider how new insights into the molecular workings of the hypoxia-triggered regulatory hierarchy could pave the way for developing flood-resilient crops.