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A unique regulatory phase of DNA methylation in the early mammalian embryo

机译:哺乳动物早期胚胎中DNA甲基化的独特调控阶段

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摘要

这项研究提供了哺乳动物胚胎生成过程中关键rn发育阶段动态DNA甲基化模式的一个高分辨率rn视图。Alexander Meissner及其同事利用“约化rn亚硫酸氢盐测序”方法,在小鼠接合体中和移rn植前胚胎生成过程的几个阶段中生成了基因组rn尺度的DNA甲基化图。这些甲基化图提供了关rn于在发育过渡过程中DNA甲基化所发生变化的rn一个碱基对分辨率的时间线。%DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly accepted that the paternal genome is actively depleted of 5-methylcytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage. However, this model is based on limited data, and so far no base-resolution maps exist to support and refine it. Here we generate genome-scale DNA methylation maps in mouse gametes and from the zygote through post-implantation. We find that the oocyte already exhibits global hypomethylation, particularly at specific families of long interspersed element 1 and long terminal repeat retroelements, which are disparately methylated between gametes and have lower methylation values in the zygote than in sperm. Surprisingly, the oocyte contributes a unique set of differentially methylated regions (DMRs)-including many CpG island promoters-that are maintained in the early embryo but are lost upon specification and absent from somatic cells. In contrast, sperm-contributed DMRs are largely intergenic and become hypermethylated after the blastocyst stage. Our data provide a genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern.
机译:这项研究提供了哺乳动物胚胎生成过程中关键rn发育阶段动态DNA甲基化模式的一个高分辨率rn视图。Alexander Meissner及其同事利用“约化rn亚硫酸氢盐测序”方法,在小鼠接合体中和移rn植前胚胎生成过程的几个阶段中生成了基因组rn尺度的DNA甲基化图。这些甲基化图提供了关rn于在发育过渡过程中DNA甲基化所发生变化的rn一个碱基对分辨率的时间线。%DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly accepted that the paternal genome is actively depleted of 5-methylcytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage. However, this model is based on limited data, and so far no base-resolution maps exist to support and refine it. Here we generate genome-scale DNA methylation maps in mouse gametes and from the zygote through post-implantation. We find that the oocyte already exhibits global hypomethylation, particularly at specific families of long interspersed element 1 and long terminal repeat retroelements, which are disparately methylated between gametes and have lower methylation values in the zygote than in sperm. Surprisingly, the oocyte contributes a unique set of differentially methylated regions (DMRs)-including many CpG island promoters-that are maintained in the early embryo but are lost upon specification and absent from somatic cells. In contrast, sperm-contributed DMRs are largely intergenic and become hypermethylated after the blastocyst stage. Our data provide a genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern.

著录项

  • 来源
    《Nature》 |2012年第7394期|p.339-344C3|共7页
  • 作者单位

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA,Department of Stem Cell and Regenerative Biology,Harvard University, Cambridge, Massachusetts 02138, USA;

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA,Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA;

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA,HowardHughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA,Department of Stem Cell and Regenerative Biology,Harvard University, Cambridge, Massachusetts 02138, USA;

  • 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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