title: LET-418/Mi2 and SPR-5/LSD1 cooperatively prevent somatic reprogramming of C. elegans germline stem cells.
abstract: Throughout their journey to forming new individuals, germline stem cells must remain totipotent, particularly by maintaining a specific chromatin structure. However, the place epigenetic factors occupy in this process remains elusive. So far, "sensitization" of chromatin by modulation of histone arrangement and/or content was believed to facilitate transcription-factor-induced germ cell reprogramming. Here, we demonstrate that the combined reduction of two epigenetic factors suffices to reprogram C. elegans germ cells. The histone H3K4 demethylase SPR-5/LSD1 and the chromatin remodeler LET-418/Mi2 function together in an early process to maintain germ cell status and act as a barrier to block precocious differentiation. This epigenetic barrier is capable of limiting COMPASS-mediated H3K4 methylation, because elevated H3K4me3 levels correlate with germ cell reprogramming in spr-5; let-418 mutants. Interestingly, germ cells deficient for spr-5 and let-418 mainly reprogram as neurons, suggesting that neuronal fate might be the first to be derepressed in early embryogenesis.
authors.affiliation: Department of Zoology, University of Fribourg, Chemin du musée 10, 1700 Fribourg, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Käser-Pébernard
authors.affiliation: Department of Zoology, University of Fribourg, Chemin du musée 10, 1700 Fribourg, Switzerland.
authors.forename: Fritz
authors.initials: F
authors.lastname: Müller
authors.affiliation: Department of Zoology, University of Fribourg, Chemin du musée 10, 1700 Fribourg, Switzerland.
authors.forename: Chantal
authors.initials: C
authors.lastname: Wicky
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D065150:Cellular Reprogramming; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008297:Male; D008745:Methylation; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism*; D009154:Mutation; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; C521495:LET-418 protein, C elegans; D010089:Oxidoreductases, N-Demethylating; C468848:SPR-5 protein, C elegans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
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