Preimplantation expression of the somatic form of Dnmt1 suggests a role in the inheritance of genomic imprints.
Preimplantation expression of the somatic form of Dnmt1 suggests a role in the inheritance of genomic imprints.
复制标题
DOI：
10.1186/1471-213x-8-9
复制
发表时间：
2008-01-25
影响因子：
--
通讯作者：
Chaillet JR
中科院分区：
文献类型：
--
作者：
Cirio MC;Ratnam S;Ding F;Reinhart B;Navara C;Chaillet JR
配子和成人中母本和父本等位基因之间相同的DNA甲基化差异表明，基因组印记的遗传严格归因于DNA甲基化的胚胎维持。这种维持与 DNA 复制的每个周期相关，包括植入前胚胎的复制周期。在卵裂期植入前小鼠胚胎中检查了 Dnmt1 胞嘧啶甲基转移酶 (Dnmt1s) 体细胞形式的表达。在 1、2、4 和 8 细胞胚胎以及桑葚和胚泡中发现了低浓度的 Dnmt1。 Dnmt1s 存在于所有阶段的细胞质中，以及除 1 细胞、原核阶段胚胎之外的所有阶段的细胞核中。相关的卵母细胞来源的 Dnmt1o 蛋白以及胚胎合成的 Dnmt1 也存在于 8 细胞胚胎的细胞核中。 1 细胞和 2 细胞胚胎中表达的 Dnmt1s 蛋白源自卵母细胞，而胚胎从 2 细胞阶段开始合成自己的 Dnmt1s。这些观察结果表明，Dnmt1s 为早期小鼠胚胎中甲基化印记的遗传提供了维持甲基转移酶活性。此外，同时合成的 Dnmt1o 和 Dnmt1s 蛋白能够替代彼此的维持功能，但卵母细胞和胚胎合成的 Dnmt1 蛋白之间缺乏功能互换，表明发育来源是植入前发育过程中 Dnmt1 功能的关键决定因素。
Identical DNA methylation differences between maternal and paternal alleles in gametes and adults suggest that the inheritance of genomic imprints is strictly due to the embryonic maintenance of DNA methylation. Such maintenance would occur in association with every cycle of DNA replication, including those of preimplantation embryos. The expression of the somatic form of the Dnmt1 cytosine methyltransferase (Dnmt1s) was examined in cleavage-stage preimplantation mouse embryos. Low concentrations of Dnmt1s are found in 1-, 2-, 4-, and 8-cell embryos, as well as in morulae and blastocysts. Dnmt1s is present in the cytoplasm at all stages, and in the nuclei of all stages except the 1-cell, pronuclear-stage embryo. The related oocyte-derived Dnmt1o protein is also present in nuclei of 8-cell embryos, along with embryo-synthesized Dnmt1s. Dnmt1s protein expressed in 1-cell and 2-cell embryos is derived from the oocyte, whereas the embryo synthesizes its own Dnmt1s from the 2-cell stage onward. These observations suggest that Dnmt1s provides maintenance methyltransferase activity for the inheritance of methylation imprints in the early mouse embryo. Moreover, the ability of Dnmt1o and Dnmt1s proteins synthesized at the same time to substitute for one another's maintenance function, but the lack of functional interchange between oocyte- and embryo-synthesized Dnmt1 proteins, suggests that the developmental source is the critical determinant of Dnmt1 function during preimplantation development.