Project description:Physiological memories of environmental stress can serve to predict future environmental changes, allowing the organism to initiate protective mechanisms and survive. Although physiological memories, or bookmarks, of environmental stress have been described in a wide range of organisms, from bacteria to plants to humans, the mechanism by which these memories persist in the absence of stress is still largely unknown. We have discovered that C. elegans transiently exposed to low doses of hydrogen sulfide (H2S) survive subsequent exposure to otherwise lethal H2S concentrations and induce H2S-responsive transcripts more robustly than naïve controls. H2S bookmarking can occur at any developmental stage and persists through cell divisions and development but is erased by fasting. We show that maintenance of the H2S bookmark requires the SET-2 histone methyltransferase and the CoREST-like demethylase complex. We propose a model in which exposure to low doses of H2S generates a long-lasting, epigenetic memory by modulating H3K4me2 modifications at specific promoters. Understanding the fundamental aspects of H2S bookmarking in this tractable system can provide mechanistic insight into how environmental exposures are translated into the epigenetic landscape in animals.
Project description:Hydrogen sulfide (H2S) is formed naturally from L-cysteine in a variety of mammalian and non-mammalian cells. To date, numerous biological effects have been ascribed to H2S including control of cardiovascular, immune and nervous function. Over or under production of H2S has been observed in several disease states including hypertension and inflammation. In addition, it has been stipulated that H2S may affect the ageing process. The model nematode Caenorhabditis elegans is ideally suited for assessing drug effects on lifespan since it is relatively short-lived, can be easily exposed to drugs and its genome is fully sequenced and widely annotated.
Project description:Hydrogen sulfide (H2S) is formed naturally from L-cysteine in a variety of mammalian and non-mammalian cells. To date, numerous biological effects have been ascribed to H2S including control of cardiovascular, immune and nervous function. Over or under production of H2S has been observed in several disease states including hypertension and inflammation. In addition, it has been stipulated that H2S may affect the ageing process. The model nematode Caenorhabditis elegans is ideally suited for assessing drug effects on lifespan since it is relatively short-lived, can be easily exposed to drugs and its genome is fully sequenced and widely annotated. The global transcriptome of control nematodes (raised using standardized laboratory conditions) was compared to nematodes exposed to 100 uM GYY4137 (morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate), a slow releasing H2S donor drug.
Project description:To elucidate the molecular mechanism underlying lifespan reduction induced by PM2.5 exposure in Caenorhabditis elegans, we performed global gene expression profiling by RNA-sequencing technology, and compared the gene expression pattern change induced by PM2.5 exposure.