Adult-specific trimethylation of histone H3 lysine 4 is prone to dynamic changes with aging in C. elegans somatic cells

Abstract

Tri-methylation on histone H3 lysine 4 (H3K4me3) is associated with active gene expression but its regulatory role in transcriptional activation is unclear. Here we used Caenorhabditis elegans to investigate the connection between H3K4me3 and gene expression regulation during aging. We uncovered around 30% of H3K4me3 enriched regions to show significant and reproducible changes with age. We further showed that these age-dynamic H3K4me3 regions largely mark gene-bodies and are acquired during adult stages. We found that these adult-specific age-dynamic H3K4me3 regions are correlated with gene expression changes with age. In contrast, H3K4me3 marking established during developmental stages remained largely stable with age, even when the H3K4me3 associated genes exhibited RNA expression changes during aging. Moreover, we found that global reduction of H3K4me3 levels results in significantly decreased RNA expression of genes that acquire H3K4me3 marking in their gene-bodies during adult stage, suggesting that altered H3K4me3 levels with age could result in age-dependent gene expression changes. Interestingly, the genes with dynamic changes in H3K4me3 and RNA levels with age are enriched for those involved in fatty acid metabolism, oxidation-reduction, and stress response. Therefore, our findings revealed divergent roles of H3K4me3 in gene expression regulation during aging, with important implications on physiological relevance.