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

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 find...

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Bibliographic Details
Published in:Genetics (Austin) 2022-05, Vol.221 (1)
Main Authors: Golden, Nicole L, Foley, Michaela K, Kim Guisbert, Karen S, Guisbert, Eric
Format: Article
Language:English
Subjects:
Animals
Caenorhabditis elegans
Caenorhabditis elegans - genetics
Caenorhabditis elegans - metabolism
Chromatin Assembly and Disassembly
Chromatin remodeling
Embryogenesis
Embryonic growth stage
Endoplasmic reticulum
Genetics
Genotoxicity
Heat shock
Homeostasis
Innate immunity
Investigation
Mi-2 Nucleosome Remodeling and Deacetylase Complex - genetics
Nematodes
Nucleosomes - genetics
Protein folding
Transcription Factors - genetics
Transcription Factors - metabolism
Transcriptomics
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Summary: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.
ISSN:1943-2631
0016-6731
1943-2631
DOI:10.1093/genetics/iyac046