H3K4 demethylase activities repress proliferative and postmitotic aging.
Bottom Line: Homeostasis of postmitotic and proliferating cells is maintained by pathways that repress stress.In addition, RBR-2 and SPR-5 were required for germ cell immortality at a high temperature.RBR-2 did not play a comparable role in the maintenance of quiescent germ cells in dauer larvae, implying that it represses stress that occurs as a consequence of germ cell proliferation, rather than stress that accumulates in nondividing cells.
Affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599-3280, USA; SPIRE Postdoctoral Fellowship Program, University of North Carolina, Chapel Hill, NC, 27599-3280, USA.Show MeSH
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Mentions: rbr-2 deficiency results in a partially penetrant Mortal Germline phenotype at 25 °C, which suggests transmission and accumulation of a heritable form of damage, or ‘proliferative aging’, of germ cells over multiple generations of growth. We tested for an analogous role of rbr-2 in the maintenance of quiescent germ cells over long periods of time using dauer larvae, a stress-induced larval stage that is long-lived. daf-2 mutants arrest development as dauer larvae at 25 °C but can resume development and produce progeny when transferred to 15 °C. Cohorts of dauer larvae for daf-2(e1370); rbr-2(ok2544) double mutants as well as daf-2(e1370) single-mutant controls were maintained at 25 °C for several months. Every 10–15 days, pools of dauers were singled and transferred to 15 °C for recovery. Both strains showed comparable levels of high viability, development to adulthood, and fertility for 60 days (Fig. 5). At 75 days, although daf-2(e1370) dauer larvae appeared paralyzed, they moved slightly when singled and showed movement on the recovery plate. However, they failed to recover at 15 °C. Unexpectedly, a high percentage of daf-2(e1370); rbr- 2(ok2544) double-mutant larvae recovered and continued to display high levels of fertility when transferred to 15 °C until day 98, at which time the experiment was terminated. In contrast, most rbr-2(ok2544) strains that had been propagated continuously at 25 °C for 98 days (28 generations) became sterile (Fig. 3B). Thus, deficiency for rbr-2 failed to compromise the maintenance of quiescent germ cells in dauer larvae. The prospect that rbr-2 function could be detrimental to longevity of daf-2-mutant dauer larvae deserves further investigation, as most studies of the effects of daf-2 on longevity concern adults. We speculate that regulation of gene expression by RBR-2 during dauer entry or dauer diapause could promote an optimal life history strategy that results in a trade-off in dauer longevity.
Affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599-3280, USA; SPIRE Postdoctoral Fellowship Program, University of North Carolina, Chapel Hill, NC, 27599-3280, USA.