Title: The Nucleosome Remodelling Factor subunit
pyp-1 negatively regulates the heat shock response upon aging in Caenorhabditis elegans Mark Noble, Andrew Deonarine, Doreen Lugano, Lori-Ann Bowie and Sandy D. Westerheide The heat shock response is a conserved eukaryotic stress response known to regulate protein homeostasis (proteostasis) and it is regulated by the transcription factor
hsf-1. Previous studies have shown tremendous effects of the HSR on life span, health span, and disease models of neurodegenerative diseases such as Alzheimer's, Parkinson and Huntington's disease. In C. elegans, proteostasis has been shown to decline with the onset of adulthood in parallel to the decline of the HSR. Therefore, understanding the molecular mechanisms and regulation of this response is vital in revealing its effects on various stresses. Recent studies have shown a link between chromatin remodelers and regulation of the heat shock response. Thus, utilizing RNAi genetic screen, we were able a uncover
pyp-1, a pyrophosphatase and subunit of the Nucleosome-remodeling factor (NURF) which showed tremendous effects on the HSR. From a different screen,
pyp-1 was also found to be a negative regulator of the heat shock response in C. elegans. We hypothesize that the age-dependent decrease in HSR induction may be due to repressive chromatin changes conferred by chromatin remodeling complexes. As a result, we identified
pyp-1 as a novel negative regulator of the heat shock response and proteostasis upon aging in C.elegans.