Regulation of stage-specific nuclear translocation of Dnmt1o during preimplantation mouse development
Regulation of stage-specific nuclear translocation of Dnmt1o during preimplantation mouse development
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DOI：
10.1006/dbio.2001.0534
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发表时间：
2002-02-15
影响因子：
2.7
通讯作者：
Schultz, RM
中科院分区：
文献类型：
--
作者：
Doherty, AS;Bartolomei, MS;Schultz, RM
通过DNA甲基转移酶1的CpG二核苷酸的DNA甲基化涉及转录的调节，特别是印迹基因的转录。虽然卵母细胞特异性形式的Dnmt 1（Dnmt 1 o）具有功能性核定位信号，它主要定位在卵母细胞和植入前小鼠胚胎的细胞质中，但在胚胎进行致密化的八细胞阶段期间经历短暂的核定位。我们在这里报告说，Dnmt 1 o可能是保留在细胞质中的一个积极的过程，因为类似于70%的DNA甲基转移酶活性保留后，透化程序，导致释放类似于75%的卵母细胞/胚胎蛋白。用破坏微丝或微管的试剂处理胚胎对透化胚胎中Dnmt 1 o的保留几乎没有影响。虽然Dnmt 1 o不与线粒体或内质网共定位，但它确实与膜联蛋白V共定位，已知膜联蛋白V与Dnmt 1 o相互作用。我们还报告说，在八细胞阶段的Dnmt 1 o的核进入的时间是独立的DNA复制，转录和蛋白质合成，以及压实，细胞接触，和胞质分裂。因此，核进入的时间似乎与受精后的时间有关，这表明分子钟控制着核输入的时间。(C)2002 Elsevier Science（美国）。
DNA methylation of CpG dinucleotides by DNA methyltransferase 1 is implicated in the regulation of transcription and, in particular, the transcription of imprinted genes. Although the oocyte-specific form of Dnmt1 (Dnmt1o) possesses a functional nuclear localization signal, it is predominantly localized in the cytoplasm of the oocyte and preimplantation mouse embryo but undergoes a transient nuclear localization during the eight-cell stage, when the embryos undergo compaction. We report here that Dnmt1o is likely retained in the cytoplasm by an active process, since similar to70% of DNA methyltransferase activity is retained following permeabilization procedures that result in the release of similar to75% of oocyte/embryo protein. Treatment of the embryos with agents that disrupt either microfilaments or microtubules has little, if any, effect on the retention of Dnmt1o in permeabilized embryos. While Dnmt1o does not colocalize with either mitochondria or endoplasmic reticulum, it does colocalize with annexin V, which is known to interact with Dnmt1o. We also report that the timing of nuclear entry of Dnmt1o during the eight-cell stage is independent of DNA replication, transcription, and protein synthesis, as well as compaction, cell contact, and cytokinesis. The time of nuclear entry, therefore, appears linked to the time following fertilization, which suggests that a molecular clock governs the time of nuclear import. (C) 2002 Elsevier Science (USA).