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Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons

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Item Type:Article
Title:Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons
Creators Name:Seelk, S. and Adrian-Kalchhauser, I. and Hargitai, B. and Hajduskova, M. and Gutnik, S. and Tursun, B. and Ciosk, R.
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.
Keywords:Notch, GLP-1, PRC2, MES, UTX-1, Stem Cell, Germline, Reprograming, Animals, Caenorhabditis elegans
Source:eLife
ISSN:2050-084X
Publisher:eLife Sciences Publications (U.K.)
Volume:5
Page Range:e15477
Date:7 September 2016
Official Publication:https://doi.org/10.7554/eLife.15477.001
PubMed:View item in PubMed

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