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Variant Histone H2afv reprograms DNA methylation during early zebrafish development

Lookup NU author(s): Laura Corbett, Dr Pier Paoli, John Casement, Professor Jelena Mann, Professor Derek Mann

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Abstract

© 2017 Taylor & Francis Group, LLCThe 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.


Publication metadata

Author(s): Madakashira B, Corbett L, Zhang C, Paoli P, Casement JW, Mann J, Sadler KC, Mann DA

Publication type: Article

Publication status: Published

Journal: Epigenetics

Year: 2017

Volume: 12

Issue: 9

Pages: 811-824

Online publication date: 03/11/2017

Acceptance date: 19/07/2017

ISSN (print): 1559-2294

ISSN (electronic): 1559-2308

Publisher: Taylor and Francis Inc.

URL: https://doi.org/10.1080/15592294.2017.1359382

DOI: 10.1080/15592294.2017.1359382


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