Maintenance of genomic methylation patterns during preimplantation development require's the somatic form of DNA methyltransferase 1
Maintenance of genomic methylation patterns during preimplantation development require's the somatic form of DNA methyltransferase 1
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DOI：
10.1016/j.ydbio.2007.10.033
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发表时间：
2008-01-01
影响因子：
2.7
通讯作者：
Kurihara, Hiroki
中科院分区：
文献类型：
--
作者：
Kurihara, Yukiko;Kawamura, Yumiko;Kurihara, Hiroki
CpG二核苷酸中胞嘧啶残基的DNA甲基化是对哺乳动物发育至关重要的表观遗传标记的组成部分。在植入前阶段的胚胎中，大部分基因组DNA被广泛地去甲基化，而甲基化模式忠实地保持在某些区域。迄今为止，除了在8细胞阶段的卵母细胞形式的DNA（胞嘧啶-5）-甲基转移酶1（Dnmt 1 o）外，还没有鉴定出在植入前发育期间负责维持DNA甲基化的酶。在此，我们证明，体细胞形式的Dnmt 1（Dnmt 1 s）是目前与染色质在MII期卵母细胞以及在整个植入前发育的细胞核。在早期的单细胞阶段，Dmm 1 s是不对称的定位在母体原核。此后，Dnmt 1 s在原核成熟过程中被募集到父本基因组中。在受精后的前两个细胞周期中，Dnmt 1 s以CRM 1/exportin依赖的方式在G2期从细胞核中输出。抗体显微注射和小干扰RNA介导的敲低减少重复脑池内A型颗粒（IAP）序列和印迹基因H19中的甲基化CpG二核苷酸。这些结果表明，Dnmt Is负责特定基因组区域的甲基化维持，其甲基化模式必须在植入前发育期间忠实地维持。(c)2007爱思唯尔公司All rights reserved.
DNA methylation at cytosine residues in CpG dinucleotides is a component of epigenetic marks crucial to mammalian development. In preimplantation stage embryos, a large part of genomic DNA is extensively demethylated, whereas the methylation patterns are faithfully maintained in certain regions. To date, no enzymes responsible for the maintenance of DNA methylation during preimplantation development have been identified except for the oocyte form of DNA (cytosine-5)-methyltransferase 1 (Dnmt 1o) at the 8-cell stage. Herein, we demonstrate that the somatic form of Dnmt 1 (Dnmt 1s) is present in association with chromatin in MII-stage oocytes as well as in the nucleus throughout preimplantation development. At the early one-cell stage, Dmm1s is asymmetrically localized in the maternal pronuclei. Thereafter, Dnmt1s is recruited to the paternal genome during pronuclear maturation. During the first two cell cycles after fertilization, Dnmt1s is exported from the nucleus in the G2 phase in a CRM1/exportin-dependent manner. Antibody microinjection and small interfering RNA-mediated knock-down decreases methylated CpG dinucleotides in repetitive intracisternal A-type particle (IAP) sequences and the imprinted gene H19. These results indicate that Dnmt Is is responsible for the maintenance methylation of particular genomic regions whose methylation patterns must be faithfully maintained during preimplantation development. (c) 2007 Elsevier Inc. All rights reserved.