斯黛拉对维持性DNA甲基化的抑制作用。
Inhibition of maintenance DNA methylation by Stella.
作者信息
Funaki Soichiro, Nakamura Toshinobu, Nakatani Tsunetoshi, Umehara Hiroki, Nakashima Hiroyuki, Nakano Toru
机构信息
Department of Pathology, Osaka University, Osaka 565-0871, Japan; Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Nagahama Institute of Bio-Science and Technology, Shiga 526-0829, Japan; JST, CREST, Saitama 332-0012, Japan.
出版信息
Biochem Biophys Res Commun. 2014 Oct 24;453(3):455-60. doi: 10.1016/j.bbrc.2014.09.101. Epub 2014 Oct 1.
DNA methylation is a key epigenetic regulator in mammals, and the dynamic balance between methylation and demethylation impacts various processes, from development to disease. DNA methylation is erased during replication when DNA methyltransferase 1 (DNMT1) fails to methylate the daughter strand, in a process known as passive DNA demethylation. We found that the enforced expression of Stella (also known as PGC7, Dppa3), a maternal factor required for the maintenance of DNA methylation in early embryos, induced global DNA demethylation in NIH3T3 cells. This demethylation was caused by the binding of Stella to Np95 (also known as Uhrf1, ICBP90) and the subsequent inhibition of DNMT1 recruitment. Considering that impaired DNA methylation profiles are associated with various developmental or disease phenomena, Stella may be a powerful tool with which to study the biological effects of global DNA hypomethylation.
DNA甲基化是哺乳动物中一种关键的表观遗传调控因子，甲基化与去甲基化之间的动态平衡影响着从发育到疾病的各种过程。当DNA甲基转移酶1（DNMT1）未能使子链甲基化时，DNA甲基化在复制过程中被消除，这一过程称为被动DNA去甲基化。我们发现，在早期胚胎中维持DNA甲基化所需的母体因子Stella（也称为PGC7、Dppa3）的强制表达，可诱导NIH3T3细胞发生全基因组DNA去甲基化。这种去甲基化是由Stella与Np95（也称为Uhrf1、ICBP90）结合以及随后对DNMT1募集的抑制引起的。鉴于DNA甲基化谱受损与各种发育或疾病现象相关，Stella可能是研究全基因组DNA低甲基化生物学效应的有力工具。
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