Elsevier

Developmental Biology

Volume 385, Issue 2, 15 January 2014, Pages 279-290
Developmental Biology

The onset of C. elegans dosage compensation is linked to the loss of developmental plasticity

https://doi.org/10.1016/j.ydbio.2013.11.001Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Gradual accumulation of dosage compensation-mediated chromatin marks in C. elegans.

  • PRC2 regulates X chromatin state in pregastrulation embryos.

  • Dosage compensation onset is coincident with loss of pluripotency.

  • PRC2 deficiency delays loss of pluripotency and the onset of dosage compensation.

  • PRC2 deficiency delays expression of dosage compensation trigger gene sdc-2.

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.

Keywords

Dosage compensation
Epigenetics
Chromatin
Pluripotency

Cited by (0)