ChIPseq examination of EAP-1 binding across generations of spr-5(by101) mutant worms

How epigenetic information is transmitted from generation to generation remains largely unknown. Deletion of the C. elegans Histone H3 lysine 4 dimethyl (H3K4me2) demethylase spr-5 leads to inherited accumulation of the euchromatic H3K4me2 mark and progressive decline in fertility. Here we identified a genetic network of chromatin-modifying factors, including the H3K4me1/me2 methyltransferases SET-17 and SET-30, the H3K9me1/me2 methyltransferase MET-2, an H3K9me3 methyltransferase, SET-26, the H3K9me3 demethylase JMJD-2, and an H3K9me reader EAP-1, which regulate the trans-generational flow of epigenetic information. Importantly, genetic ablation of set-17, set-30, jmjd-2, or eap-1 suppresses the progressive transgenerational phenotypes, while loss of SET-26 or MET-2 accelerates the infertility of spr-5 mutant worms. We further show that loss of spr-5 also causes a trans-generational increase in lifespan, which is dependent on these chromatin regulators as well as DAF-36 and DAF-12, which control a germline to soma longevity signaling pathway. These findings suggest that the balance between the euchromatic H3K4 and the heterochromatic H3K9 methylation regulates trans-generational effects on longevity and fertility.