Divergent regulatory roles of NuRD chromatin remodeling complex subunits GATAD2 and CHD4 in Caenorhabditis elegans

Abstract

Abstract During proteotoxic stress, a pathway known as the heat shock response 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 heat shock response. Here, we extend these findings to show that dcp-66 positively regulates the heat shock response at the cellular, molecular, and organismal levels. As GATAD2 is a subunit of the nucleosome remodeling and deacetylase chromatin remodeling complex, we examined other nucleosome remodeling and deacetylase subunits and found that the let-418 (CHD4) nucleosome repositioning core also regulates the heat shock response. However, let-418 acts as a negative regulator of the heat shock response, in contrast to positive regulation by dcp-66. The divergent effects of these two nucleosome remodeling and deacetylase subunits extend to the regulation of other stress responses including oxidative, genotoxic, and endoplasmic reticulum 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 nucleosome remodeling and deacetylase subunits in organismal physiology. We incorporate these findings into a molecular model whereby different mechanisms of recruitment to promoters can result in the divergent effects of nucleosome remodeling and deacetylase subunits.