Advanced genomics identifies growth effectors for proteotoxic ER stress recovery in Arabidopsis thaliana

Adverse environmental and pathophysiological situations can overwhelm the biosynthetic capacity of the endoplasmic reticulum (ER), igniting a potentially lethal condition known as ER stress. ER stress results in growth reduction and the activation of a conserved cytoprotective signaling cascade, the unfolded protein response (UPR), to mitigate ER stress. As ER stress subsides, growth is resumed; however, despite a pivotal role of the UPR in growth restoration, the underlying mechanisms are yet unknown. To discover these, we undertook a genomics approach and mined the gene reprogramming roles of the two critical and conserved UPR modulators, basic leucine zipper28 (bZIP28) and bZIP60 in ER stress resolution. Through a coexpression-based network modeling and experimental validation, we identified key responsive genes acting downstream of the UPR bZIP-transcription factors (bZIP-TF), and demonstrated their roles in organ growth during recovery from ER stress. Our analyses have also set up a novel pipeline for functional gene discovery in ER stress resolution with broad applicability across multicellular eukaryotes. For RNA-seq analysis, a total of 54 samples, which consists of 3 genotypes under 2 treatments at 3 time-points in 3 biological replicates, were processed. For ChIP-seq analysis, a total of 48 samples, which consists of 2 proteins with 2 treatment at 3 time-points in 2 biological replicates, were processed.