Advanced genomics identifies growth effectors for proteotoxic ER stress recovery in Arabidopsis thaliana. 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. Overall design: 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.