In C. elegans, the germline is set apart from somatic lineages early and requires the MES proteins for survival and proper development. The MES proteins are a group of chromatin regulators named for their Maternal Effect Sterile phenotype. It is well established that epigenetic mechanisms are involved in specifying and maintaining cell fates, yet it is still unclear if and how epigenetic marks are transmitted across generations and maintained through cell divisions. We are investigating the MES proteins and the histone modifications they generate to elucidate the mechanisms by which epigenetic information is transmitted from parents to progeny and to daughter chromosomes during DNA replication. We previously reported that MES-4 transmits an epigenetic ‘memory of germline’ from mother’s germ cells to embryos, likely to guide gene expression in the primordial germ cells. MES-4 is a histone methyltransferase that catalyzes tri-methylation on Lys 36 of Histone H3 (H3K36me3), a mark associated with active transcription. Our data support a model in which MES-4 and H3K36me3 transmit a ‘memory of germline gene expression’ by maintaining marking in embryos of genes expressed in the maternal germline regardless of their expression status in embryos. We have used immunostaining to demonstrate that 1) H3K36me3 is delivered to embryos on the chromosomes from both the oocyte and the sperm, 2) MES-4 is delivered to embryos solely through the oocyte, 3) the recruitment of maternally supplied MES-4 to sperm chromosomes in the zygote requires that those chromosomes were marked with H3K36me3 during spermatogenesis, and 4) H3K36me3 inherited in the absence of MES-4 disappears after two rounds of DNA replication. Together, these results reveal that maternal MES-4 is required to maintain inherited H3K36me3 in early embryos. Remarkably, MES-4 maintains H3K36me3 in a gamete-of-origin manner: when H3K36me3 is inherited on the chromosomes from only one gamete, that pattern of half-marked/half-unmarked chromosomes persists through multiple rounds of cell division. Persistence of this gamete-of-origin pattern in early embryos suggests that MES-4 maintains the ‘memory of germline’ by propagating inherited H3K36me3 on germline-expressed genes. Our findings show that epigenetic information in the form of modified histones is transmitted to the embryo by both gametes, and is faithfully maintained through multiple rounds of DNA replication in the early embryo by maternally loaded enzyme. This epigenetic information is essential for primordial germ cell survival and development.
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