Histone H2AFX Links Meiotic Chromosome Asynapsis to Prophase I Oocyte Loss in Mammals

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Chromosome abnormalities, such as aneuploidies and structural variants (i.e. translocations, inversions), are strikingly common in the human population, causing disorders such as Down syndrome and Turner syndrome. One important consequence of chromosome abnormalities in mammals is errors during meiosis, the specialized cell division that generates sperm and eggs for reproduction. As a result of these meiotic errors, patients with chromosome abnormalities oftentimes suffer from infertility due to loss of developing germ cells. The precise molecular mechanism for germ cell losses and infertility due to chromosome abnormalities is not well understood, but is hypothesized to result from a surveillance mechanism, which has evolved to prevent aneuploidies from developing from abnormal germ cells. In mammals, meiotic surveillance mechanisms have been hypothesized to monitor for unrepaired DNA double-strand breaks (DSB) and/or chromosome pairing/synapsis errors. Here we test these hypotheses using a variety of chromosomally variant mouse models. We find that germ cell loss in female mice with chromosome abnormalities is dependent on phosphorylation of the histone variant H2AFX, an epigenetic mark involved in the transcriptional silencing of asynapsed chromosomes during meiosis. These data inform a silencing-based mechanism of germ cell loss in patients with chromosome abnormalities and for the prophase I surveillance system which safeguards against aneuploidy.

Vyšlo v časopise: Histone H2AFX Links Meiotic Chromosome Asynapsis to Prophase I Oocyte Loss in Mammals. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005462
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005462

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