title: The onset of C. elegans dosage compensation is linked to the loss of developmental plasticity.
abstract: Dosage compensation (DC) equalizes X-linked gene expression between sexes. In Caenorhabditis elegans, the dosage compensation complex (DCC) localizes to both X chromosomes in hermaphrodites and downregulates gene expression 2-fold. The DCC first localizes to hermaphrodite X chromosomes at the 30-cell stage, coincident with a developmental transition from plasticity to differentiation. To test whether DC onset is linked to loss of developmental plasticity, we established a timeline for the accumulation of DC-mediated chromatin features on X (depletion of histone H4 lysine 16 acetylation (H4K16ac) and enrichment of H4K20 monomethylation (H4K20me1)) in both wild type and developmentally delayed embryos. Surprisingly, we found that H4K16ac is depleted from the X even before the 30-cell stage in a DCC-independent manner. This depletion requires the activities of MES-2, MES-3, and MES-6 (a complex similar to the Polycomb Repressive Complex 2), and MES-4. By contrast, H4K20me1 becomes enriched on X chromosomes several cell cycles after DCC localization to the X, suggesting that it is a late mark in DC. MES-2 also promotes differentiation, and mes-2 mutant embryos exhibit prolonged developmental plasticity. Consistent with the hypothesis that the onset of DC is linked to differentiation, DCC localization and H4K20me1 accumulation on the X chromosomes are delayed in mes mutant hermaphrodite embryos. Furthermore, the onset of hermaphrodite-specific transcription of sdc-2 (which triggers DC) is delayed in mes-2 mutants. We propose that as embryonic blastomeres lose their developmental plasticity, hermaphrodite X chromosomes transition from a MES protein-regulated state to DCC-mediated repression.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N. University Ave., Ann Arbor, MI 48109-1048, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Custer
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N. University Ave., Ann Arbor, MI 48109-1048, USA.
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Snyder
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N. University Ave., Ann Arbor, MI 48109-1048, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Flegel
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N. University Ave., Ann Arbor, MI 48109-1048, USA. Electronic address: gyorgyi@umich.edu.
authors.forename: Györgyi
authors.initials: G
authors.lastname: Csankovszki
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D004303:Dosage Compensation, Genetic; D017403:In Situ Hybridization; D008297:Male; D034622:RNA Interference
chemical_list: D002843:Chromatin
keywords: Chromatin; Dosage compensation; Epigenetics; Pluripotency