title: Transdifferentiation. Sequential histone-modifying activities determine the robustness of transdifferentiation.
abstract: Natural interconversions between distinct somatic cell types have been reported in species as diverse as jellyfish and mice. The efficiency and reproducibility of some reprogramming events represent unexploited avenues in which to probe mechanisms that ensure robust cell conversion. We report that a conserved H3K27me3/me2 demethylase, JMJD-3.1, and the H3K4 methyltransferase Set1 complex cooperate to ensure invariant transdifferentiation (Td) of postmitotic Caenorhabditis elegans hindgut cells into motor neurons. At single-cell resolution, robust conversion requires stepwise histone-modifying activities, functionally partitioned into discrete phases of Td through nuclear degradation of JMJD-3.1 and phase-specific interactions with transcription factors that have conserved roles in cell plasticity and terminal fate selection. Our results draw parallels between epigenetic mechanisms underlying robust Td in nature and efficient cell reprogramming in vitro.
authors.affiliation: Department of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Université de Strasbourg, 67404 Illkirch CU Strasbourg, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Zuryn
authors.affiliation: Department of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Université de Strasbourg, 67404 Illkirch CU Strasbourg, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ahier
authors.affiliation: Institut Curie, INSERM U934, CNRS UMR3215, 26, Rue d'Ulm, 75005 Paris, France.
authors.forename: Manuela
authors.initials: M
authors.lastname: Portoso
authors.affiliation: Department of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Université de Strasbourg, 67404 Illkirch CU Strasbourg, France.
authors.forename: Esther Redhouse
authors.initials: ER
authors.lastname: White
authors.affiliation: Department of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Université de Strasbourg, 67404 Illkirch CU Strasbourg, France.
authors.forename: Marie-Charlotte
authors.initials: MC
authors.lastname: Morin
authors.affiliation: Institut Curie, INSERM U934, CNRS UMR3215, 26, Rue d'Ulm, 75005 Paris, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Margueron
authors.affiliation: Department of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Université de Strasbourg, 67404 Illkirch CU Strasbourg, France. sophie@igbmc.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Jarriault
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054337:Cell Dedifferentiation; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D054338:Cell Transdifferentiation; D004064:Digestive System / Q000166:cytology; D056466:Histone Demethylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008954:Models, Biological; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D006657:Histones; D014157:Transcription Factors; C112508:unc-3 protein, C elegans; D056466:Histone Demethylases; C000591647:JMJD-3.1 protein, C elegans; D011495:Histone-Lysine N-Methyltransferase; C464501:Set-1 protein, C elegans; D008239:Lysine