4.7 Article

JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress

Journal

SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-21914-9

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Funding

  1. Danish Cancer Society [30826]
  2. Fondazione Umberto Veronesi
  3. Swiss National Science Foundation
  4. Danish National Research Council [DNRF82]
  5. Novo Nordisk Foundation [2010p-A14073, NNF16OC0022718]

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Post-translational modifications of histones, constitutive components of chromatin, regulate chromatin compaction and control all DNA-based cellular processes. C. elegans JMJD-1.2, a member of the KDM7 family, is a demethylase active towards several lysine residues on Histone 3 (H3), but its contribution in regulating histone methylation in germ cells has not been fully investigated. Here, we show that jmjd-1.2 is expressed abundantly in the germline where it controls the level of histone 3 lysine 9, lysine 23 and lysine 27 di-methylation (H3K9/K23/K27me2) both in mitotic and meiotic cells. Loss of jmjd-1.2 is not associated with major defects in the germ cells in animals grown under normal conditions or after DNA damage induced by UV or ionizing irradiation. However, jmjd-1.2 mutants are more sensitive to replication stress and the progeny of mutant animals exposed to hydroxyurea show increased embryonic lethality and mutational rate, compared to wild-type. Thus, our results suggest a role for jmjd-1.2 in the maintenance of genome integrity after replication stress and emphasize the relevance of the regulation of histone methylation in genomic stability.

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