Divergent Regulatory Roles of NuRD Chromatin Remodeling Complex Subunits GATAD2 and CHD4 in Caenorhabditis elegans

Abstract

During stress, a protective cellular network known as the heat shock response (HSR) is induced to maintain protein-folding homeostasis, or proteostasis. While the HSR is essential for stress resistance, its misregulation is associated with neurodegenerative disease and cancer. Using the nematode model organism Caenorhabditis elegans, we have identified the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylase) as a novel regulator of the HSR. Here, we begin with a brief introduction of the HSR and chromatin remodeling complexes in C. elegans, prior to presenting our findings in a series of two chapters. In chapter one, we outline a set of standardized protocols for facilitating accurate measurement of the HSR in C. elegans. In chapter two, we show that dcp-66 and let-418 subunits of the NuRD complex regulate the HSR in divergent ways. This paradigm extends to other stress responses and even to other pathways. Together, this work highlights the power of using C. elegans as a biological tool to discover novel genetic interactions important in physiology and disease.