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首页> 外文期刊>Nature >Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition
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Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition

机译：单核Hi-C在卵母细胞到合子转变时显示出独特的染色质重组

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摘要

Chromatin is reprogrammed after fertilization to produce a totipotent zygote with the potential to generate a new organism(1). The maternal genome inherited from the oocyte and the paternal genome provided by sperm coexist as separate haploid nuclei in the zygote. How these two epigenetically distinct genomes are spatially organized is poorly understood. Existing chromosome conformation capture-based methods(2-5) are not applicable to oocytes and zygotes owing to a paucity of material. To study three-dimensional chromatin organization in rare cell types, we developed a single-nucleus Hi-C (high-resolution chromosome conformation capture) protocol that provides greater than tenfold more contacts per cell than the previous method(2). Here we show that chromatin architecture is uniquely reorganized during the oocyte-to-zygote transition in mice and is distinct in paternal and maternal nuclei within single-cell zygotes. Features of genomic organization including compartments, topologically associating domains (TADs) and loops are present in individual oocytes when averaged over the genome, but the presence of each feature at a locus varies between cells. At the sub-megabase level, we observed stochastic clusters of contacts that can occur across TAD boundaries but average into TADs. Notably, we found that TADs and loops, but not compartments, are present in zygotic maternal chromatin, suggesting that these are generated by different mechanisms. Our results demonstrate that the global chromatin organization of zygote nuclei is fundamentally different from that of other interphase cells. An understanding of this zygotic chromatin 'ground state' could potentially provide insights into reprogramming cells to a state of totipotency.
机译：受精后染色质被重新编程以产生全能合子，并有可能产生新的生物（1）。从卵母细胞继承的母体基因组和精子提供的母体基因组在合子中作为单独的单倍体核共存。这两个表观遗传学上不同的基因组如何在空间上组织得很少。现有的基于染色体构象捕获的方法（2-5）由于缺乏材料而不适用于卵母细胞和受精卵。为了研究稀有细胞类型中的三维染色质组织，我们开发了单核Hi-C（高分辨率染色体构象捕获）协议，该协议可为每个细胞提供比以前的方法多十倍的联系（2）。在这里，我们显示染色质结构在小鼠卵母细胞向合子过渡期间是唯一重组的，并且在单细胞合子内的父本和母本核中是不同的。在基因组上平均时，单个卵母细胞中存在基因组组织的特征，包括区室，拓扑关联结构域（TAD）和环，但是每个特征在细胞之间的存在都不同。在亚兆数据库级别，我们观察到了可能跨越TAD边界但平均到TAD中的联系的随机群集。值得注意的是，我们发现在合子母体染色质中存在TAD和环，但不存在区室，表明它们是由不同的机制产生的。我们的结果表明，合子核的全球染色质组织与其他间期细胞的根本不同。对这种合子染色质“基态”的了解可能会为将细胞重编程为全能状态提供见识。

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  • 来源
    《Nature》 |2017年第7648期|110-114|共5页
  • 作者

    Flyamer Ilya M.; Gassler Johanna; Imakaev Maxim; Brandao Hugo B.; Ulianov Sergey V.; Abdennur Nezar; Razin Sergey V.; Mirny Leonid A.; Tachibana-Konwalski Kikue;

  • 作者单位

    Austrian Acad Sci, Vienna Bioctr VBC, IMBA Inst Mol Biotechnol, Dr Bohr Gasse 3, A-1030 Vienna, Austria|Russian Acad Sci, Inst Gene Biol, Moscow 119334, Russia|Lomonosov Moscow State Univ, Fac Biol, Moscow 119234, Russia|Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland;

    Austrian Acad Sci, Vienna Bioctr VBC, IMBA Inst Mol Biotechnol, Dr Bohr Gasse 3, A-1030 Vienna, Austria;

    MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA|MIT, Dept Phys, Cambridge, MA 02139 USA;

    Harvard Univ, Harvard Program Biophys, Cambridge, MA 02138 USA;

    Russian Acad Sci, Inst Gene Biol, Moscow 119334, Russia|Lomonosov Moscow State Univ, Fac Biol, Moscow 119234, Russia;

    MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA;

    Russian Acad Sci, Inst Gene Biol, Moscow 119334, Russia|Lomonosov Moscow State Univ, Fac Biol, Moscow 119234, Russia;

    MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA|MIT, Dept Phys, Cambridge, MA 02139 USA|Harvard Univ, Harvard Program Biophys, Cambridge, MA 02138 USA;

    Austrian Acad Sci, Vienna Bioctr VBC, IMBA Inst Mol Biotechnol, Dr Bohr Gasse 3, A-1030 Vienna, Austria;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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