Conserved and nuanced hierarchy of gene regulatory response to hypoxia.

A dynamic assembly of nuclear and cytoplasmic processes regulate gene activity. Hypoxic stress and the associated energy crisis activate a plurality of regulatory mechanisms including modulation of chromatin structure, transcriptional activation and post-transcriptional processes. Temporal control of genes is associated with specific chromatin modifications and transcription factors. Genome-scale technologies that resolve transcript subpopulations in the nucleus and cytoplasm indicate post-transcriptional processes enable cells to conserve energy, prepare for prolonged stress and accelerate recovery. Moreover, the harboring of gene transcripts associated with growth in the nucleus and macromolecular RNA-protein complexes contributes to the preferential translation of stress-responsive gene transcripts during hypoxia. We discuss evidence of evolutionary variation in integration of nuclear and cytoplasmic processes that may contribute to variations in flooding resilience.