4.5 Article

Caenorhabditis elegans Dosage Compensation Regulates Histone H4 Chromatin State on X Chromosomes

Journal

MOLECULAR AND CELLULAR BIOLOGY
Volume 32, Issue 9, Pages 1710-1719

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.06546-11

Keywords

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Funding

  1. National Institutes of Health [RO1 GM079533]
  2. National Science Foundation [MCB 1021013]
  3. University of Michigan
  4. NIH National Center for Research Resources
  5. Direct For Biological Sciences
  6. Div Of Molecular and Cellular Bioscience [1021013] Funding Source: National Science Foundation

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Dosage compensation equalizes X-linked gene expression between the sexes. This process is achieved in Caenorhabditis elegans by hermaphrodite-specific, dosage compensation complex (DCC)-mediated, 2-fold X chromosome downregulation. How the DCC downregulates gene expression is not known. By analyzing the distribution of histone modifications in nuclei using quantitative fluorescence microscopy, we found that H4K16 acetylation (H4K16ac) is underrepresented and H4K20 monomethylation (H4K20me1) is enriched on hermaphrodite X chromosomes in a DCC-dependent manner. Depletion of H4K16ac also requires the conserved histone deacetylase SIR-2.1, while enrichment of H4K20me1 requires the activities of the histone methyltransferases SET-1 and SET-4. Our data suggest that the mechanism of dosage compensation in C. elegans involves redistribution of chromatin-modifying activities, leading to a depletion of H4K16ac and an enrichment of H4K20me1 on the X chromosomes. These results support conserved roles for histone H4 chromatin modification in worm dosage compensation analogous to those seen in flies, using similar elements and opposing strategies to achieve differential 2-fold changes in X-linked gene expression.

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