Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Nat Commun. 2019 Aug 23;10(1):3821. doi: 10.1038/s41467-019-11820-7.
Meiosis is the specialized cell division during which parental genomes recombine to create genotypically unique gametes. Despite its importance, mammalian meiosis cannot be studied in vitro, greatly limiting mechanistic studies. In vivo, meiocytes progress asynchronously through meiosis and therefore the study of specific stages of meiosis is a challenge. Here, we describe a method for isolating pure sub-populations of nuclei that allows for detailed study of meiotic substages. Interrogating the H3K4me3 landscape revealed dynamic chromatin transitions between substages of meiotic prophase I, both at sites of genetic recombination and at gene promoters. We also leveraged this method to perform the first comprehensive, genome-wide survey of histone marks in meiotic prophase, revealing a heretofore unappreciated complexity of the epigenetic landscape at meiotic recombination hotspots. Ultimately, this study presents a straightforward, scalable framework for interrogating the complexities of mammalian meiosis.
减数分裂是一种特殊的细胞分裂过程，在此过程中亲本基因组发生重组，产生基因型独特的配子。尽管减数分裂非常重要，但哺乳动物的减数分裂无法在体外进行研究，这极大地限制了对其机制的研究。在体内，减数分裂细胞会异步进行，因此研究特定的减数分裂阶段是一个挑战。在这里，我们描述了一种分离纯亚群核的方法，该方法可用于详细研究减数分裂前期的亚期。研究 H3K4me3 图谱揭示了在遗传重组位点和基因启动子处，减数分裂前期亚期之间的动态染色质转变。我们还利用这种方法首次进行了全面的、全基因组范围内的减数分裂前期组蛋白标记调查，揭示了在减数分裂重组热点处，表观遗传景观的复杂性以前未被认识到。最终，这项研究提出了一种简单、可扩展的框架，用于研究哺乳动物减数分裂的复杂性。
