Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans

PLoS Genet. 2015 Dec 7;11(12):e1005698. doi: 10.1371/journal.pgen.1005698. eCollection 2015 Dec.


In Caenorhabditis elegans, the dosage compensation complex (DCC) specifically binds to and represses transcription from both X chromosomes in hermaphrodites. The DCC is composed of an X-specific condensin complex that interacts with several proteins. During embryogenesis, DCC starts localizing to the X chromosomes around the 40-cell stage, and is followed by X-enrichment of H4K20me1 between 100-cell to comma stage. Here, we analyzed dosage compensation of the X chromosome between sexes, and the roles of dpy-27 (condensin subunit), dpy-21 (non-condensin DCC member), set-1 (H4K20 monomethylase) and set-4 (H4K20 di-/tri-methylase) in X chromosome repression using mRNA-seq and ChIP-seq analyses across several developmental time points. We found that the DCC starts repressing the X chromosomes by the 40-cell stage, but X-linked transcript levels remain significantly higher in hermaphrodites compared to males through the comma stage of embryogenesis. Dpy-27 and dpy-21 are required for X chromosome repression throughout development, but particularly in early embryos dpy-27 and dpy-21 mutations produced distinct expression changes, suggesting a DCC independent role for dpy-21. We previously hypothesized that the DCC increases H4K20me1 by reducing set-4 activity on the X chromosomes. Accordingly, in the set-4 mutant, H4K20me1 increased more from the autosomes compared to the X, equalizing H4K20me1 level between X and autosomes. H4K20me1 increase on the autosomes led to a slight repression, resulting in a relative effect of X derepression. H4K20me1 depletion in the set-1 mutant showed greater X derepression compared to equalization of H4K20me1 levels between X and autosomes in the set-4 mutant, indicating that H4K20me1 level is important, but X to autosomal balance of H4K20me1 contributes slightly to X-repression. Thus H4K20me1 is not only a downstream effector of the DCC [corrected].In summary, X chromosome dosage compensation starts in early embryos as the DCC localizes to the X, and is strengthened in later embryogenesis by H4K20me1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics*
  • Carrier Proteins / genetics*
  • Chromatin / genetics
  • Dosage Compensation, Genetic*
  • Embryonic Development*
  • Female
  • Histone-Lysine N-Methyltransferase / genetics*
  • Male
  • Mutation
  • Nuclear Proteins / genetics*
  • X Chromosome / genetics


  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Chromatin
  • DPY-21 protein, C elegans
  • DPY-27 protein, C elegans
  • Nuclear Proteins
  • Histone-Lysine N-Methyltransferase
  • SET-4 protein, C elegans
  • Set-1 protein, C elegans

Associated data

  • GEO/GSE67650