Liu Yang, Maekawa Toshio, Yoshida Keisuke, Kaneda Hideki, Chatton Bruno, Wakana Shigeharu, Ishii Shunsuke
Laboratory of Molecular Genetics RIKEN Tsukuba Institute Japan.
Department of Molecular Genetics and Ph.D. Program in Human Biology School of Integrative and Global Majors University of Tsukuba Japan.
FEBS Open Bio. 2017 Sep 11;7(10):1598-1610. doi: 10.1002/2211-5463.12304. eCollection 2017 Oct.
Assisted reproductive technologies, including fertilization (IVF), are now frequently used, and increasing evidence indicates that IVF causes gene expression changes in children and adolescents that increase the risk of metabolic diseases. Although such gene expression changes are thought to be due to IVF-induced epigenetic changes, the mechanism remains elusive. We tested whether the transcription factor ATF7-which mediates stress-induced changes in histone H3K9 tri- and dimethylation, typical marks of epigenetic silencing-is involved in the IVF-induced gene expression changes. IVF up- and downregulated the expression of 688 and 204 genes, respectively, in the liver of 3-week-old wild-type (WT) mice, whereas 87% and 68% of these were not changed, respectively, by IVF in ATF7-deficient ( ) mice. The genes, which are involved in metabolism, such as pyrimidine and purine metabolism, were upregulated in WT mice, but not in mice. Of the genes whose expression was upregulated by IVF in WT mice, 37% were also upregulated by a loss of ATF7. These results indicate that ATF7 is a key factor in establishing the memory of IVF effects on metabolic pathways.
包括体外受精（IVF）在内的辅助生殖技术如今被频繁使用，越来越多的证据表明，体外受精会导致儿童和青少年的基因表达发生变化，从而增加患代谢性疾病的风险。尽管这种基因表达变化被认为是由体外受精诱导的表观遗传变化所致，但其机制仍不清楚。我们测试了转录因子ATF7（它介导应激诱导的组蛋白H3K9三甲基化和二甲基化变化，这是表观遗传沉默的典型标志）是否参与了体外受精诱导的基因表达变化。在3周龄野生型（WT）小鼠的肝脏中，体外受精分别上调和下调了688个和204个基因的表达，而在ATF7缺陷型（ ）小鼠中，这些基因中分别有87%和68%未因体外受精而发生变化。参与代谢（如嘧啶和嘌呤代谢）的基因在野生型小鼠中上调，但在 小鼠中未上调。在野生型小鼠中因体外受精而上调表达的基因中，37%也因ATF7缺失而上调。这些结果表明，ATF7是建立体外受精对代谢途径影响记忆的关键因素。
