title: A histone H4 lysine 20 methyltransferase couples environmental cues to sensory neuron control of developmental plasticity.
abstract: Animals change developmental fates in response to external cues. In the nematodeCaenorhabditis elegans, unfavorable environmental conditions induce a state of diapause known as dauer by inhibiting the conserved DAF-2 insulin-like signaling (ILS) pathway through incompletely understood mechanisms. We have previously established a role for theC. elegansdosage compensation protein DPY-21 in the control of dauer arrest and DAF-2 ILS. Here, we show that the histone H4 lysine 20 methyltransferase SET-4, which also influences dosage compensation, promotes dauer arrest in part by repressing the X-linkedins-9gene, which encodes a new agonist insulin-like peptide (ILP) expressed specifically in the paired ASI sensory neurons that are required for dauer bypass.ins-9repression in dauer-constitutive mutants requires DPY-21, SET-4 and the FoxO transcription factor DAF-16, which is the main target of DAF-2 ILS. By contrast, autosomal genes encoding major agonist ILPs that promote reproductive development are not repressed by DPY-21, SET-4 or DAF-16/FoxO. Our results implicate SET-4 as a sensory rheostat that reinforces developmental fates in response to environmental cues by modulating autocrine and paracrine DAF-2 ILS.
authors.affiliation: Departments of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Colin E
authors.initials: CE
authors.lastname: Delaney
authors.affiliation: Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Albert T
authors.initials: AT
authors.lastname: Chen
authors.affiliation: Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Jacqueline V
authors.initials: JV
authors.lastname: Graniel
authors.affiliation: Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Dumas
authors.affiliation: Departments of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA patrick.j.hu@vanderbilt.edu.|Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.|Institute of Gerontology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Patrick J
authors.identifier: 0000-0002-5611-8062
authors.initials: PJ
authors.lastname: Hu
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004777:Environment; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D050172:Genes, X-Linked; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D007814:Larva / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity; D011984:Sensory Receptor Cells / Q000502:physiology*; D012727:Sex Characteristics; D059467:Transcriptome / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D006657:Histones; D011495:Histone-Lysine N-Methyltransferase; C577070:SET-4 protein, C elegans; D008239:Lysine
keywords: C. elegans; Dauer; Dosage compensation; FoxO; H4K20; Insulin-like peptides