A histone H4 lysine 20 methyltransferase couples environmental cues to sensory neuron control of developmental plasticity.
Animals change developmental fates in response to external cues. In the nematode Caenorhabditis 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 the C. elegans dosage 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-linked ins-9 gene, which encodes a new agonist insulin-like peptide (ILP) expressed specifically in the paired ASI sensory neurons that are required for dauer bypass. ins-9 repression 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.
['Delaney|Colin E|CE|', 'Chen|Albert T|AT|', 'Graniel|Jacqueline V|JV|', 'Dumas|Kathleen J|KJ|', 'Hu|Patrick J|PJ|0000-0002-5611-8062']
D000818:Animals D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D004777:Environment D005260:Female D020869:Gene Expression Profiling D018507:Gene Expression Regulation, Developmental D050172:Genes, X-Linked D011495:Histone-Lysine N-Methyltransferase D006657:Histones D007814:Larva D008239:Lysine D008297:Male D008954:Models, Biological D009154:Mutation D009473:Neuronal Plasticity D011984:Sensory Receptor Cells D012727:Sex Characteristics D059467:Transcriptome
Dauer C. elegans Dosage compensation Insulin-like peptides FoxO H4K20