Genome-wide analysis of DNA methylation dynamics during early human development.
Genome-wide analysis of DNA methylation dynamics during early human development.
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早期人类发育过程中DNA甲基化动力学的全基因组分析。
DOI：
10.1371/journal.pgen.1004868
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发表时间：
2014-12
期刊：
影响因子：
4.5
通讯作者：
Arima T
中科院分区：
文献类型：
--
作者：
Okae H;Chiba H;Hiura H;Hamada H;Sato A;Utsunomiya T;Kikuchi H;Yoshida H;Tanaka A;Suyama M;Arima T
在哺乳动物着床前发育过程中，DNA甲基化是全局重编程的，这对正常发育至关重要。最近亚硫酸盐还原测序（RRBS）研究表明，甲基组动力学在人类和小鼠早期胚胎之间基本上是保守的。已知RRBS覆盖了所有基因组cpg的5-10%，有利于富含cpg区域的RRBS。为了获得人类早期发育过程中甲基组的公正和更完整的代表，我们对覆盖所有基因组CpGs的70%的人类配子和囊胚进行了全基因组亚硫酸盐测序。我们发现，与小鼠囊胚相比，人类囊胚中母体基因组的去甲基化程度要小得多，这可能导致人类基因组中印迹差异甲基化区域的数量增加。父本基因组的整体去甲基化被证实，但发现SINE-VNTR-Alu元件和一些其他串联重复序列的区域被特异性地保护免受这种整体去甲基化。此外，着丝粒卫星重复序列在人类卵母细胞中高度甲基化，而在小鼠卵母细胞中则没有，这可能是由于新生DNA甲基转移酶的差异表达所致。这些数据强调了在哺乳动物早期发育过程中DNA甲基化的保守和物种特异性调控。我们的工作为理解早期人类发育过程中分化和多能性的表观遗传过程提供了进一步的关键信息。受精后DNA甲基化重编程对哺乳动物的正常发育至关重要。早期胚胎对环境压力敏感，许多报告指出，与辅助生殖技术相关的DNA甲基化错误风险增加。因此，了解人类早期发育过程中正常的DNA甲基化模式是非常重要的。最近亚硫酸氢盐测序研究报道了人类配子和早期胚胎的部分甲基组。为了更全面地了解人类早期发育过程中的DNA甲基化动力学，我们报道了人类配子和囊胚的全基因组亚硫酸盐测序。我们发现，在囊胚中，父亲基因组整体去甲基化，而母亲基因组去甲基化的程度要小得多。我们还揭示了早期人类发育过程中印迹差异甲基化区域、基因体和重复序列的独特调控。我们的高分辨率甲基组图谱对于理解人类卵母细胞的表观遗传重编程至关重要，并将有助于人类胚胎的着床前表观遗传学诊断。
DNA methylation is globally reprogrammed during mammalian preimplantation development, which is critical for normal development. Recent reduced representation bisulfite sequencing (RRBS) studies suggest that the methylome dynamics are essentially conserved between human and mouse early embryos. RRBS is known to cover 5–10% of all genomic CpGs, favoring those contained within CpG-rich regions. To obtain an unbiased and more complete representation of the methylome during early human development, we performed whole genome bisulfite sequencing of human gametes and blastocysts that covered>70% of all genomic CpGs. We found that the maternal genome was demethylated to a much lesser extent in human blastocysts than in mouse blastocysts, which could contribute to an increased number of imprinted differentially methylated regions in the human genome. Global demethylation of the paternal genome was confirmed, but SINE-VNTR-Alu elements and some other tandem repeat-containing regions were found to be specifically protected from this global demethylation. Furthermore, centromeric satellite repeats were hypermethylated in human oocytes but not in mouse oocytes, which might be explained by differential expression of de novo DNA methyltransferases. These data highlight both conserved and species-specific regulation of DNA methylation during early mammalian development. Our work provides further information critical for understanding the epigenetic processes underlying differentiation and pluripotency during early human development. DNA methylation reprogramming after fertilization is critical for normal mammalian development. Early embryos are sensitive to environmental stresses and a number of reports have pointed out the increased risk of DNA methylation errors associated with assisted reproduction technologies. Therefore, it is very important to understand normal DNA methylation patterns during early human development. Recent reduced representation bisulfite sequencing studies reported partial methylomes of human gametes and early embryos. To provide a more comprehensive view of DNA methylation dynamics during early human development, we report on whole genome bisulfite sequencing of human gametes and blastocysts. We show that the paternal genome is globally demethylated in blastocysts whereas the maternal genome is demethylated to a much lesser extent. We also reveal unique regulation of imprinted differentially methylated regions, gene bodies and repeat sequences during early human development. Our high-resolution methylome maps are essential to understand epigenetic reprogramming by human oocytes and will aid in the preimplantation epigenetic diagnosis of human embryos.
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影响因子：
16
作者：
Proudhon, Charlotte;Duffie, Rachel;Ajjan, Sophie;Cowley, Michael;Iranzo, Julian;Carbajosa, Guillermo;Saadeh, Heba;Holland, Michelle L.;Oakey, Rebecca J.;Rakyan, Vardhman K.;Schulz, Reiner;Bourc'his, Deborah
通讯作者：
Bourc'his, Deborah
影响因子：
14.5
作者：
Hancks DC;Kazazian HH Jr
通讯作者：
Kazazian HH Jr
影响因子：
4.5
作者：
Kobayashi H;Sakurai T;Imai M;Takahashi N;Fukuda A;Yayoi O;Sato S;Nakabayashi K;Hata K;Sotomaru Y;Suzuki Y;Kono T
通讯作者：
Kono T
影响因子：
56.9
作者：
Bourc'his, D;Xu, GL;Bestor, TH
通讯作者：
Bestor, TH
影响因子：
4.4
作者：
Das R;Lee YK;Strogantsev R;Jin S;Lim YC;Ng PY;Lin XM;Chng K;Yeo GSh;Ferguson-Smith AC;Ding C
通讯作者：
Ding C