Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos
Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos
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DOI：
10.4161/epi.6.12.18206
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发表时间：
2011-12-01
期刊：
影响因子：
3.7
通讯作者：
Aoki, Fugaku
中科院分区：
文献类型：
--
作者：
Nashun, Buhe;Akiyama, Tomohiko;Aoki, Fugaku
当分化的体细胞核移植到去核卵母细胞中时，其基因组被重塑为全能状态。为了阐明这种基因组重塑的机制，我们分析了核移植胚胎中核心组蛋白变体组成的变化，因为最近的证据表明，染色质结构可以作为变体组蛋白替换的结果而重塑。我们发现供体细胞来源的组蛋白H3变体H3.1、H3.2和H3.3以及H2A和H2A.Z从移植到去核卵母细胞的核的染色质中迅速消除。伴随着这种去除，卵母细胞储存的组蛋白H3变体和H2A。X掺入到移植的细胞核中，而H2A和H2A.Z的掺入是最小的或未检测到。这些变异组蛋白的掺入是DNA复制无关的。这些结果表明，大多数核心组蛋白H2A和H3组分在供体细胞核和受体细胞质之间动态交换，这进一步表明，用卵母细胞储存的组蛋白替换供体细胞组蛋白可能在核移植胚胎的基因组重塑中起关键作用。此外，核移植胚胎中所有组蛋白变体的掺入模式与受精胚胎中几乎相同。只有H3.1的掺入模式不同，它被纳入移植供体核，但不是在受精胚胎的原核。这一结果表明，H3.1的掺入对基因组重塑过程具有不利影响，并导致体细胞核克隆的低成功率。
The genome of differentiated somatic nuclei is remodeled to a totipotent state when they are transplanted into enucleated oocytes. To clarify the mechanism of this genome remodeling, we analyzed changes in the composition of core histone variants in nuclear-transferred embryos, since recent evidence has revealed that chromatin structure can be remodeled as a result of variant histone replacement. We found that the donor cell-derived histone H3 variants H3.1, H3.2 and H3.3, as well as H2A and H2A.Z, were rapidly eliminated from the chromatin of nuclei transplanted into enucleated oocytes. Accompanying this removal, oocyte-stored histone H3 variants and H2A. X were incorporated into the transplanted nuclei, while the incorporation of H2A and H2A.Z was minimal or not detected. The incorporation of these variant histones was DNA replication-independent. These results suggest that most core histone H2A and H3 components are dynamically exchanged between donor nuclei and recipient cytoplasm, which further suggests that replacement of donor cell histones with oocyte-stored histones may play a key role in genome remodeling in nuclear-transferred embryos. In addition, the incorporation patterns of all of the histone variants in the nuclear-transferred embryos were virtually the same as in the fertilized embryos. Only the incorporation pattern of H3.1 differed; it was incorporated into the transplanted donor nuclei, but not in the pronuclei of fertilized embryos. This result suggests that the incorporation of H3.1 has a detrimental effect on the process of genome remodeling and contributes to the low success rate of somatic nuclear cloning.