Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons
- Max-Delbrück-Center for Molecular Medicine, Germany
- Friedrich Miescher Institute for Biomedical Research, Switzerland
Abstract
Cell-fate reprograming is at the heart of development, yet very little is known about the molecular mechanisms promoting or inhibiting reprograming in intact organisms. In the C. elegans germline, reprograming germ cells into somatic cells requires chromatin perturbation. Here, we describe that such reprograming is facilitated by GLP-1/Notch signaling pathway. This is surprising, since this pathway is best known for maintaining undifferentiated germline stem cells/progenitors. Through a combination of genetics, tissue-specific transcriptome analysis, and functional studies of candidate genes, we uncovered a possible explanation for this unexpected role of GLP-1/Notch. We propose that GLP-1/Notch promotes reprograming by activating specific genes, silenced by the Polycomb repressive complex 2 (PRC2), and identify the conserved histone demethylase UTX-1 as a crucial GLP-1/Notch target facilitating reprograming. These findings have wide implications, ranging from development to diseases associated with abnormal Notch signaling.
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Author details
Funding
European Research Council (ERC-2014-STG #637530 - REPROWORM)
- Baris Tursun
Helmholtz-Gemeinschaft (MDC PhD)
- Stefanie Seelk
European Research Council (FP7-PEOPLE-2012-CIG #333922- REPROL53U48)
- Baris Tursun
European Cooperation in Science and Technology (SBFI C15.0038)
- Rafal Ciosk
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Seelk et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons
eLife 5:e15477.
https://doi.org/10.7554/eLife.15477
