LAUSR

During proteotoxic stress, a pathway known as the heat shock response (HSR) is induced to maintain protein-folding homeostasis, or proteostasis. Previously, we identified the Caenorhabditis elegans GATAD2 ortholog, dcp-66, as a novel regulator of the HSR. Here, we extend these findings to show that dcp-66 positively regulates the HSR at the cellular, molecular, and organismal levels. As GATAD2 is a subunit of the NuRD chromatin remodeling complex, we examined other NuRD subunits and found that the let-418 (CHD4) nucleosome repositioning core also regulates the HSR. However, let-418 acts as a negative regulator of the HSR, in contrast to positive regulation by dcp-66. The divergent effects of these two NuRD subunits extend to the regulation of other stress responses including oxidative, genotoxic, and ER stress. Furthermore, a transcriptomic approach reveals additional divergently regulated pathways, including innate immunity and embryogenesis. Taken together, this work establishes new insights into the role of NuRD subunits in organismal physiology. We incorporate these findings into a molecular model whereby different mechanisms of NuRD recruitment to promoters can result in the divergent effects of NuRD subunits.