Notch signaling is essential for maintaining stem cells of self-renewing tissues but also for regulating differentiation during development. We observed such seemingly disparate roles of Notch in the germline where it maintains stem cells but also promotes germ cell reprogramming to neurons upon ectopic transcription factor expression. But how maintenance of stem cells and promoting differentiation can be employed simultaneously by Notch signaling remains unclear. Depletion of the histone-chaperone gene lin-53 allows conversion of germ cells into neurons (Tursun et al., 2011). LIN-53 is part of different chromatin-regulating complexes such as the Polycomb repressive complex 2 (PRC2) and we previously demonstrated that LIN-53 protects germ cells together with PRC2 (Patel et al., 2012). Here, we show that this germline conversion depends on the Notch receptor gene glp-1 and is significantly enhanced when Notch signaling is increased. Germ cell conversion is increased upon depletion of lin-53 or PRC2 members in the glp-1 gain-of function (gf) mutant ar202. To rule out that this effect is simply due to increased numbers of mitotic germ cells in the glp-1 (gf) background we used a gld-1/gld-2/glp-1(lf) triple mutant which lacks glp-1 Notch-signaling but has proliferating mitotic germ cells. In this background conversion into neurons is abolished attesting the requirement for Notch signaling during germ cell conversion in lin-53 or PRC2-depleted germline. In order to understand the role of Notch signaling in germ cell reprogramming we performed transcriptome analysis from dissected gonads. Our analysis revealed that Notch signaling mediates reactivation of genes repressed by PRC2. A number of Notch-activated genes regulate self-renewal and differentiation suggesting that Notch controls germ cell development by antagonizing PRC2-mediated repression and this counteraction against PRC2 activity leads to enhancement of germ cell reprogramming to neurons. Furthermore, we identified the chromodomain protein MRG-1 as another barrier for cellular reprogramming of germ cells. Interestingly increased Notch signaling in glp-1 ar202 worms also enhances reprogramming into neuron-like cells in mrg-1 depleted germ cells. However, glp-1 is not required for the germ cell conversion in mrg-1 RNAi worms suggesting that MRG-1 might play a role in protecting germ cells independently of PRC2. Our findings demonstrate that the germline stem cell niche controls cell behavior by signaling through the Notch pathway to chromatin.
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