Abstract
Germ cell immortality, or transgenerational maintenance of the germ line, could be promoted by mechanisms that could occur in either mitotic or meiotic germ cells. Here we report for the first time that the GSP-2 PP1/Glc7 phosphatase promotes germ cell immortality. Small RNA-induced genome silencing is known to promote germ cell immortality, and we identified a separation-of-function allele of C. elegans gsp-2 that is compromised for germ cell immortality and is also defective for small RNA-induced genome silencing and meiotic but not mitotic chromosome segregation. Previous work has shown that GSP-2 is recruited to meiotic chromosomes by LAB-1, which also promoted germ cell immortality. At the generation of sterility, gsp-2 and lab-1 mutant adults displayed germline degeneration, univalents, histone methylation and histone phosphorylation defects in oocytes, phenotypes that mirror those observed in sterile small RNA-mediated genome silencing mutants. Our data suggest that a meiosis-specific function of GSP-2 ties small RNA-mediated silencing of the epigenome to germ cell immortality. We also show that transgenerational epigenomic silencing at hemizygous genetic elements requires the GSP-2 phosphatase, suggesting a functional link to small RNAs. Given that LAB-1 localizes to the interface between homologous chromosomes during pachytene, we hypothesize that small localized discontinuities at this interface could promote genomic silencing in a manner that depends on small RNAs and the GSP-2 phosphatase.
Highlights
Animals, including humans, are comprised of two broad cell types: somatic cells and germ cells
Loss of germ cell immortality can result from mutations that disrupt small RNAmediated genome silencing, which protects the germ line from foreign genetic elements such as transposons
We report for the first time that the C. elegans protein phosphatase GSP-2 that promotes core chromosome biology functions during meiosis is required for germ cell immortality
Summary
Animals, including humans, are comprised of two broad cell types: somatic cells and germ cells. In C. elegans, disruption of pathways that promote germ cell immortality results in initially fertile animals that become sterile after reproduction for a number of generations. Many such mortal germline (mrt) mutant strains are temperature-sensitive, becoming sterile at 25 ̊C but remaining fertile indefinitely at 20 ̊C [2]. One nuclear RNAi defective mutant, nrde-2, a number of heritable RNAi mutants, including hrde-1, and two RNAi defective mutants, rsd-2 and rsd-6, only become sterile after growth for multiple generations at the restrictive temperature of 25 ̊C [10,12,13,14,15,16] The reason for this temperature-sensitivity is not clear. The transgenerational fertility defects of such mutants could reflect a progressive desilencing of heterochromatin, which is modulated by histone modifications that occur in response to small RNAs, such as H3K4 demethylation and H3K9me2/3 [15,19]
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