Lee, Siu Sylvia et al. (2019) International Worm Meeting "Links between altered fat metabolism and lifespan in different types of self-sterility in C. elegans."

Chaturbedi, Amaresh, Lee, Siu Sylvia

[International Worm Meeting, 2019]

We are interested in how reproduction impacts fat metabolism and longevity. It has been well known that the germline stem cells in C. elegans signal to modulate longevity and altered fat metabolism is likely part of the underlying mechanism. We are comparing different classes of mutations that cause self-sterility in C. elegans, and found that whereas these other mutants accumulate excess fat, they do not enjoy a lifespan benefit. Comparing these various sterile mutants may help to delineate the unique mechanism that germline stem cells have on fat regulation and longevity.

Wang, Wenke et al. (2017) International Worm Meeting "The Role of SET-9 and SET-26 in Longevity and Germline Function."

Chaturbedi, Amaresh, Lee , Siu, Wang, Wenke

[International Worm Meeting, 2017]

Epigenetic mechanisms, including histone modifications, have been found to regulate both aging and germline function. We discovered two highly homologous SET domain containing proteins, SET-9 and SET-26, to regulate lifespan and germline function in C. elegans. Specifically, lacking somatic set-26 extends lifespan, whereas deficiency of both set-9 and set-26 causes a severe germline defect. Both SET-9 and SET-26 have a PHD domain and a SET domain. We showed that the PHD domains of SET-9 and SET-26 bind to H3K4me3 in vitro and the genomic distributions of SET-9 and SET-26 are highly correlated with H3K4me3 marking in vivo, supporting a model that SET-9 and SET-26 are recruited to H3K4me3 marked regions in C. elegans. Although previous report suggested that the SET domain of SET-26 can deposit H3K9me3 in vitro, we found that loss of set-9 and set-26 does not affect global H3K9me3 levels. On the other hand, we detected elevated levels and expansion of H3K4me3 marking around SET-9 & SET-26 binding sites in the set-9 set-26 double mutant, suggesting that SET-9 & SET-26 normally help to restrict H3K4me3 marking. Interestingly, the spreading of H3K4me3 was not associated with gene expression changes. On the other hand, we revealed that some of the loci bound by SET-9 & SET-26 show gene expression changes in the set-9 set-26 mutants. We conclude that SET-9 & SET-26 may have dual roles in regulating gene expression and in restricting H3K4me3 deposition.