Topic: H3K9me3

Recent evidence suggests that epigenetic mechanisms may contribute to memory deficits in aging. Specifically, in the hippocampus, the repressive epigenetic mark H3K9me3 (tri-methylated lysine 9 on histone H3) has been implicated in the silencing of genes essential for memory. Yet, the impact of the age-related increased H3K9me3 levels on neuronal function remains unclear. We hypothesized that H3K9me3 accumulation renders neurons refractory to stimulation. To assess the influence of H3K9me3 on neuronal activation, we reduced H3K9me3 levels by silencing the major methyltransferase responsible to

PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that regulate gene expression, yet their molecular functions in neurobiology are unclear. While investigating neurodegeneration mechanisms using human α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg pan-neuronal overexpressing strains, we unexpectedly observed dysregulation of piRNAs. RNAi screening revealed that knock-down of piRNA biogenesis genes improved thrashing behavior; further, a tofu-1 gene deletion ameliorated phenotypic deficits in α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg transgenic strains. piRNA expression was extensively downregulated and