PUBLICATION

Variant Histone H2afv Reprograms DNA Methylation During Early Zebrafish Development

Authors
Madakashira, B., Corbett, L., Zhang, C., Paoli, P., Casement, J.W., Mann, J., Sadler, K.C., Mann, D.A.
ID
ZDB-PUB-171104-2
Date
2017
Source
Epigenetics   12(9): 811-824 (Journal)
Registered Authors
Sadler Edepli, Kirsten C., Zhang, Chi
Keywords
none
MeSH Terms
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Animals
  • DNA Methylation*
  • Genetic Variation
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology
  • Histones/metabolism*
  • Phenotype
  • DNA (Cytosine-5-)-Methyltransferase 1/genetics
  • DNA (Cytosine-5-)-Methyltransferase 1/physiology
(all 12)
PubMed
29099280 Full text @ Epigenetics
Abstract
The DNA methylome is re-patterned during discrete phases of vertebrate development. In zebrafish, there are two waves of global DNA demethylation and re-methylation: the first occurs prior to gastrulation when the parental methylome is changed to the zygotic pattern and the second occurs after formation of the embryonic body axis, during organ specification. The occupancy of the histone variant H2A.Z and regions of DNA methylation are generally anti-correlated, and it has been proposed that H2A.Z restricts the boundaries of highly methylated regions. While many studies have described the dynamics of methylome changes during early zebrafish development, the factors involved in establishing the DNA methylation landscape in zebrafish embryos have not been identified. We test the hypothesis that the zebrafish ortholog of H2A.Z (H2afv) restricts DNA methylation during development. We find that in control embryos, bulk genome methylation decreases after gastrulation, with a nadir at the bud stage and peaks during mid-somitogenesis and by 24 hours post-fertilization, total DNA methylation levels return to that detected in gastrula. Early zebrafish embryos depleted of H2afv have significantly more bulk DNA methylation during somitogenesis, suggesting that H2afv limits methylation during this stage of development. H2afv deficient embryos are small, with multisystemic abnormalities. Genetic interaction experiments demonstrate that these phenotypes are suppressed by depletion of DNA methyltransferase 1 (Dnmt1). This work demonstrates that H2afv is essential for global DNA methylation reprogramming during early vertebrate development and that embryonic development requires crosstalk between H2afv and Dnmt1.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
No data available
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz15TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    dnmt1MO4-dnmt1MRPHLNO
    h2az2bMO1-h2az2bMRPHLNO
    tp53MO4-tp53MRPHLNO
    1 - 3 of 3
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    Fish
    Antibodies
    Name Type Antigen Genes Isotypes Host Organism
    Ab1-h2afvapolyclonal
      Rabbit
      1 - 1 of 1
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      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      DsRedEFGDsRed
      EGFPEFGEGFP
      1 - 2 of 2
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      Mapping
      No data available