Integrated multiomic analysis from chromatin to translation of stimulus-regulated gene activity exposes dominant patterns of nuclear-level control

Abstract

Gene regulation is modulated from chromatin to translation. To better understand the integration of nuclear and cytoplasmic gene regulatory dynamics, we performed a multi-omic survey of the epigenome through the translatome of the response of Arabidopsis seedlings to hypoxia and reoxygenation. This included eight assays of chromatin (histones, accessibility, RNAPII and transcription factor binding) and three assays of RNA (nuclear, polyadenylated, and ribosome-associated). Dynamic patterns of nuclear regulation distinguished stress-induced and growth-associated mRNAs. The rapid upregulation of hypoxia-responsive gene transcripts and their preferential translation was accompanied by increased chromatin accessibility, RNAPII engagement and reduced Histone 2A.Z association. The more progressive upregulation of heat stress gene transcripts was characterized by early engagement of RNAPII and elevation of nuclear over polyadenylated RNA. Promoters of the rapidly versus progressively upregulated gene cohorts were enriched for cis-elements of ethylene-responsive and heat shock factor transcription factor families, respectively. By contrast, genes associated with growth including ribosomal proteins underwent distinct histone modifications, yet retained RNAPII engagement and accumulated nuclear transcripts during the stress. Upon reaeration, many of the progressively upregulated and growth-associated gene transcripts were mobilized to ribosomes. Thus, multi-level nuclear regulation distinguishes transcript synthesis, accumulation and translation in response to a transient stress.