RNA sequencing-based identification of aberrant imprinting in cloned mice
RNA sequencing-based identification of aberrant imprinting in cloned mice
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DOI：
10.1093/hmg/ddt495
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发表时间：
2014-02-15
影响因子：
3.5
通讯作者：
Arima, Takahiro
中科院分区：
文献类型：
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作者：
Okae, Hiroaki;Matoba, Shogo;Arima, Takahiro
体细胞核移植（SCNT）克隆动物为理解核表观遗传重编程到全能性状态的机制提供了一个独特的模型。尽管许多表型异常已在克隆动物中得到证实，但其潜在机制尚不清楚。在这项研究中，我们在克隆小鼠的大脑和胎盘组织中进行了转录组全等位基因表达分析。我们发现，Gab1、Sfmbt2和Slc38a4在所有克隆小鼠中都出现了印迹缺失，这可能与克隆小鼠胎盘增大有关。这三个基因在生长的卵母细胞中不需要从头DNA甲基化来建立印迹，这意味着涉及从头DNA甲基化无关的机制。在近一半的克隆小鼠胚胎中也观察到Dlk1-Dio3印迹的缺失，并显示出与胚胎致死性很强的相关性。我们的发现对于理解克隆动物发育异常的潜在机制至关重要。我们还强调，应该特别关注特定的印迹基因，用于SCNT的治疗和农业应用。
Animals cloned by somatic cell nuclear transfer (SCNT) provide a unique model for understanding the mechanisms of nuclear epigenetic reprograming to a state of totipotency. Though many phenotypic abnormalities have been demonstrated in cloned animals, the underlying mechanisms are not well understood. In this study, we performed transcriptome-wide allelic expression analyses in brain and placental tissues of cloned mice. We found that Gab1, Sfmbt2 and Slc38a4 showed loss of imprinting in all cloned mice analyzed, which might be involved in placentomegaly of cloned mice. These three genes did not require de novo DNA methylation in growing oocytes for the establishment of imprinting, implying the involvement of a de novo DNA methylation-independent mechanism. Loss of Dlk1-Dio3 imprinting was also observed in nearly half of cloned mouse embryos and showed a strong correlation with embryonic lethality. Our findings are essential to understand the underlying mechanisms of developmental abnormalities of cloned animals. We also emphasize that particular attention should be paid to specific imprinted genes for therapeutic and agricultural applications of SCNT.