Regulation of H3K9me3 during preimplantation development†
Regulation of H3K9me3 during preimplantation development†
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DOI：
10.1093/biolre/ioy201
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发表时间：
2018-09
影响因子：
3.6
通讯作者：
F. Aoki
中科院分区：
文献类型：
--
作者：
F. Aoki
受精后，受精卵获得全能性，即分化成任何类型细胞的能力。胚胎在植入前发育过程中失去了这种能力。在这些过程中，基因表达模式和染色质结构会动态变化 [1, 2]。与这些变化相伴的是，表观遗传修饰发生了巨大的变化，这种变化至少部分地导致了基因表达和染色质结构的变化以及全能性的丧失[3]。这些表观遗传修饰之一 H3K9me3 已被证明在异染色质形成和各种类型细胞（包括植入前胚胎）基因表达抑制中发挥重要作用 [4, 5]。此外，据报道，降低H3K9me3的水平可以提高体细胞核转移到去核卵母细胞中的重编程效率，这表明H3K9me3是胚胎可塑性的决定因素之一[6]。尽管H3K9me3在植入前胚胎中的功能已被深入研究，但这种表观遗传修饰的调节机制尚不清楚。范恒宇实验室最近在EMBO杂志上发表的一篇论文[7]报道，CRL4泛素E3连接酶的接头DCAF13参与植入前胚胎中H3K9me3的调控。作者表明，DCAF13 表达在 8 细胞至桑葚胚阶段增加。此外，Dcaf13 敲除 (KO) 导致 SUV39H1 和 H3K9me3 水平增加，并导致桑葚胚阶段前胚胎发育停滞。因此，作者认为 DCAF13 通过泛素途径降解 SUV39H1 来调节 H3K9me3，并在植入前发育中发挥重要作用。
After fertilization, zygotes acquire totipotency, the ability to differentiate into any type of cell. Embryos lose this ability during preimplantation development. Over the course of these processes, gene expression patterns and chromatin structures change dynamically [1, 2]. Concomitantly with these changes, epigenetic modifications drastically shift, a change that is at least partially responsible for changes in gene expression and chromatin structure and the loss of totipotency [3]. One of these epigenetic modifications, H3K9me3, has been shown to play important roles in heterochromatin formation and repression of gene expression in various types of cells, including preimplantation embryos [4, 5]. Furthermore, it has been reported that decreasing the level of H3K9me3 improves the efficiency of reprogramming in somatic cell nuclei transferred to enucleated oocytes, suggesting that H3K9me3 is one of the determinants of embryo plasticity [6]. Although the functions of H3K9me3 in preimplantation embryos have been thoroughly investigated, the mechanisms by which this epigenetic modification is regulated are not well understood.A recent paper published in EMBO Journal, by Heng-Yu Fan’s laboratory [7] reported that DCAF13, an adaptor of CRL4 ubiquitin E3 ligase, is involved in the regulation of H3K9me3 in preimplantation embryos. The authors showed that DCAF13 expression increases at the 8-cell to morula stage. Furthermore, Dcaf13 knockout (KO) caused an increase in SUV39H1 and H3K9me3 levels and developmental arrest of embryos before the morula stage. The authors thus suggested that DCAF13 regulates H3K9me3 by degrading SUV39H1 via the ubiquitin pathway and plays an important role in preimplantation development.