Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans

作者：Chenglin Li, Mintie Pu, Wenke Wang, Amaresh Chaturbedi, Felicity J. Emerson, Siu Sylvia Lee · 发表于：PLoS Genetics · 年份：2021 · DOI：10.1371/journal.pgen.1009432 · 被引用次数：26 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、Genomics and Chromatin Dynamics、RNA Research and Splicing

Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In this study, we aimed to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. We focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed region-specific gain and loss of both histone marks, but the changes are more evident for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most statistically significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed "aging-specific repressive regions" (ASRRs). These ASRRs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Maintenance of high H3K9me2 levels in these regions have been shown to correlate with a longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed natur...