Variant Histone H2afv reprograms DNA methylation during early zebrafish development

Bhavani Madakashira, Laura Corbett, Chi Zhang, Pier Paoli, John W. Casement, Jelena Mann, Kirsten Sadler Edepli, Derek A. Mann

    Research output: Contribution to journalArticle

    Abstract

    The DNA methylome is re-patterned during discrete phases of vertebrate development. In zebrafish, there are 2 waves of global DNA demethylation and re-methylation: the first occurs before 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; by 24 hours post -fertilization, total DNA methylation levels return to those 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.

    Original languageEnglish (US)
    Pages (from-to)811-824
    Number of pages14
    JournalEpigenetics
    Volume12
    Issue number9
    DOIs
    StatePublished - Sep 2 2017

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    Zebrafish
    DNA Methylation
    Histones
    Embryonic Structures
    Methylation
    Gastrulation
    DNA
    Methyltransferases
    Vertebrates
    Z-Form DNA
    Gastrula
    Fertilization
    Embryonic Development
    Genome
    Phenotype

    ASJC Scopus subject areas

    • Molecular Biology
    • Cancer Research

    Cite this

    Madakashira, B., Corbett, L., Zhang, C., Paoli, P., Casement, J. W., Mann, J., ... Mann, D. A. (2017). Variant Histone H2afv reprograms DNA methylation during early zebrafish development. Epigenetics, 12(9), 811-824. https://doi.org/10.1080/15592294.2017.1359382

    Variant Histone H2afv reprograms DNA methylation during early zebrafish development. / Madakashira, Bhavani; Corbett, Laura; Zhang, Chi; Paoli, Pier; Casement, John W.; Mann, Jelena; Sadler Edepli, Kirsten; Mann, Derek A.

    In: Epigenetics, Vol. 12, No. 9, 02.09.2017, p. 811-824.

    Research output: Contribution to journalArticle

    Madakashira, B, Corbett, L, Zhang, C, Paoli, P, Casement, JW, Mann, J, Sadler Edepli, K & Mann, DA 2017, 'Variant Histone H2afv reprograms DNA methylation during early zebrafish development', Epigenetics, vol. 12, no. 9, pp. 811-824. https://doi.org/10.1080/15592294.2017.1359382
    Madakashira B, Corbett L, Zhang C, Paoli P, Casement JW, Mann J et al. Variant Histone H2afv reprograms DNA methylation during early zebrafish development. Epigenetics. 2017 Sep 2;12(9):811-824. https://doi.org/10.1080/15592294.2017.1359382
    Madakashira, Bhavani ; Corbett, Laura ; Zhang, Chi ; Paoli, Pier ; Casement, John W. ; Mann, Jelena ; Sadler Edepli, Kirsten ; Mann, Derek A. / Variant Histone H2afv reprograms DNA methylation during early zebrafish development. In: Epigenetics. 2017 ; Vol. 12, No. 9. pp. 811-824.
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