MicroRNA-125b is a key epigenetic regulatory factor that promotes nuclear transfer reprogramming.
MicroRNA-125b is a key epigenetic regulatory factor that promotes nuclear transfer reprogramming.
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MicroRNA-125b是促进核转移重编程的关键表观遗传调控因子
DOI：
10.1074/jbc.m117.796771
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发表时间：
2017-09-22
期刊：
影响因子：
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通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Zhang J;Qu P;Zhou C;Liu X;Ma X;Wang M;Wang Y;Su J;Liu J;Zhang Y
体细胞核移植(SCNT)介导的重编程是一种快速、高效和复杂的过程，将分化的体细胞重编程为多能状态。然而，这一复杂的重新编程过程中的许多因素在很大程度上仍然未知。在这里，我们报告了microRNA(MiR)miR-125b是SCNT介导的重编程的重要组成部分。荧光素酶报告基因分析、定量聚合酶链式反应和Western blotting结果表明，miR-125b能直接结合编码组蛋白赖氨酸N-甲基转移酶SUV39H1的3‘非翻译区，下调SCNT胚胎中组蛋白H3赖氨酸-9三甲基化(H3K9me3)。此外，miR-125b/SUV39H1相互作用导致SUV39H1介导的H3K9me3丢失，引起异染色质松弛，促进SCNT胚胎的发育。SCNT卵裂球的转录组分析表明，HNF1 Homeobox B(HNF1B)基因编码miR-125b/SUV39H1轴下游的转录因子，在赋予植入前胚胎发育能力方面具有重要作用。我们得出结论，miR-125b通过靶向SUV39H1来减少抑制性H3K9me3修饰的沉积，从而促进SCNT介导的核重新编程。
Somatic cell nuclear transfer (SCNT)-mediated reprogramming is a rapid, efficient, and sophisticated process that reprograms differentiated somatic cells to a pluripotent state. However, many factors in this elaborate reprogramming process remain largely unknown. Here, we report that the microRNA (miR) miR-125b is an important component of SCNT-mediated reprogramming. Luciferase reporter assay, quantitative PCR, and Western blotting demonstrated that miR-125b directly binds the 3′-untranslated region of SUV39H1, encoding the histone-lysine N-methyltransferase SUV39H1, to down-regulate histone H3 lysine-9 tri-methylation (H3K9me3) in SCNT embryos. Furthermore, the miR-125b/SUV39H1 interaction induced loss of SUV39H1-mediated H3K9me3, caused heterochromatin relaxation, and promoted the development of SCNT embryos. Transcriptome analyses of SCNT blastomeres indicated that HNF1 homeobox B (HNF1B), a gene encoding a transcription factor downstream of and controlled by the miR-125b/SUV39H1 axis, is important for conferring developmental competence on preimplantation embryos. We conclude that miR-125b promotes SCNT-mediated nuclear reprogramming by targeting SUV39H1 to decrease the deposition of repressive H3K9me3 modifications.