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首页> 外文期刊>Nature >DNA methylation on N-6-adenine in mammalian embryonic stem cellse
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DNA methylation on N-6-adenine in mammalian embryonic stem cellse

机译：哺乳动物胚胎干细胞中N-6-腺嘌呤的DNA甲基化

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摘要

It has been widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes. Here we identify N-6-methyladenine as another form of DNA modification in mouse embryonic stem cells. Alkbh1 encodes a demethylase for N-6-methyladenine. An increase of N-6-methyladenine levels in Alkbh1-deficient cells leads to transcriptional silencing. N-6-methyladenine deposition is inversely correlated with the evolutionary age of LINE-1 transposons; its deposition is strongly enriched at young (<1.5 million years old) but not old (>6 million years old) L1 elements. The deposition of N-6-methyladenine correlates with epigenetic silencing of such LINE-1 transposons, together with their neighbouring enhancers and genes, thereby resisting the gene activation signals during embryonic stem cell differentiation. As young full-length LINE-1 transposons are strongly enriched on the X chromosome, genes located on the X chromosome are also silenced. Thus, N-6-methyladenine developed a new role in epigenetic silencing in mammalian evolution distinct from its role in gene activation in other organisms. Our results demonstrate that N-6-methyladenine constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes.
机译：已经广泛接受5-甲基胞嘧啶是哺乳动物基因组中DNA甲基化的唯一形式。在这里，我们确定N-6-甲基腺嘌呤是小鼠胚胎干细胞中DNA修饰的另一种形式。 Alkbh1编码N-6-甲基腺嘌呤的脱甲基酶。 Alkbh1缺陷细胞中N-6-甲基腺嘌呤水平的升高导致转录沉默。 N-6-甲基腺嘌呤的沉积与LINE-1转座子的进化年龄成反比。它的沉积物在年轻（<150万岁）的L1元素上非常丰富，但在老（> 600万岁）的L1元素上却不丰富。 N-6-甲基腺嘌呤的沉积与这种LINE-1转座子及其邻近的增强子和基因的表观遗传沉默有关，从而在胚胎干细胞分化过程中抵抗基因激活信号。当年轻的全长LINE-1转座子在X染色体上高度富集时，位于X染色体上的基因也被沉默。因此，N-6-甲基腺嘌呤在哺乳动物进化中的表观遗传沉默中发挥了新的作用，与其在其他生物中的基因激活作用不同。我们的结果表明，N-6-甲基腺嘌呤构成哺乳动物基因组表观遗传调控库的关键组成部分。

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  • 来源
    《Nature》 |2016年第7599期|329-333|共5页
  • 作者

    Wu Tao P.; Wang Tao; Seetin Matthew G.; Lai Yongquan; Zhu Shijia; Lin Kaixuan; Liu Yifei; Byrum Stephanie D.; Mackintosh Samuel G.; Zhong Mei; Tackett Alan; Wang Guilin; Hon Lawrence S.; Fang Gang; Swenberg James A.; Xiao Andrew Z.;

  • 作者单位

    Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA|Yale Univ, Sch Med, Yale Stem Cell Ctr, 333 Cedar St, New Haven, CT 06520 USA;

    Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA|Yale Univ, Sch Med, Yale Stem Cell Ctr, 333 Cedar St, New Haven, CT 06520 USA;

    Pacific Biosci, 1380 Willow Rd, Menlo Pk, CA 94025 USA;

    Univ N Carolina, Environm Sci & Engn, Chapel Hill, NC 27599 USA;

    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA|Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA;

    Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA|Yale Univ, Sch Med, Yale Stem Cell Ctr, 333 Cedar St, New Haven, CT 06520 USA;

    Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA|Yale Univ, Sch Med, Yale Stem Cell Ctr, 333 Cedar St, New Haven, CT 06520 USA;

    Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA;

    Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA;

    Yale Univ, Sch Med, Yale Stem Cell Ctr, 333 Cedar St, New Haven, CT 06520 USA|Yale Univ, Sch Med, Dept Cell Biol, 333 Cedar St, New Haven, CT 06520 USA;

    Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA;

    Yale Univ, Sch Med, Yale Ctr Genome Anal, Dept Mol Biophys & Biochem, 333 Cedar St, New Haven, CT 06520 USA;

    Pacific Biosci, 1380 Willow Rd, Menlo Pk, CA 94025 USA;

    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA|Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA;

    Univ N Carolina, Environm Sci & Engn, Chapel Hill, NC 27599 USA;

    Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA|Yale Univ, Sch Med, Yale Stem Cell Ctr, 333 Cedar St, New Haven, CT 06520 USA;

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