A Histone Methylation Network Regulates Transgenerational Epigenetic Memory in C. elegans

• H3K9me regulators control transgenerational sterility of spr-5, an H3K4me2 demethylase
• H3K4me2 increases and H3K9me3 declines in spr-5 mutant worms across generations
• Loss of H3K4 methyltransferases suppress transgenerational sterility of spr-5 mutants

SummaryHow 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 multiple chromatin-modifying factors, including H3K4me1/me2 and H3K9me3 methyltransferases, an H3K9me3 demethylase, and an H3K9me reader, which either suppress or accelerate the progressive transgenerational phenotypes of spr-5 mutant worms. Our findings uncover a network of chromatin regulators that control the transgenerational flow of epigenetic information and suggest that the balance between euchromatic H3K4 and heterochromatic H3K9 methylation regulates transgenerational effects on fertility.

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