Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells
Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells
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DOI：
10.1093/emboj/16.21.6510
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发表时间：
1997-11-03
期刊：
影响因子：
11.4
通讯作者：
Surani, MA
中科院分区：
文献类型：
--
作者：
Tada, M;Tada, T;Surani, MA
原始生殖细胞（PGCs）的基因组重编程（包括全基因组去甲基化）防止异常的表观遗传修饰传递给后代。该过程还确保同源染色体在雌性和雄性生殖系中的可印记基因座中适当转换之前首先获得相同的表观遗传状态。胚胎生殖细胞（EG）具有与PGCs相似的表观基因型。我们用EG细胞通过分析EG-胸腺淋巴细胞杂交细胞中对体细胞核的影响来研究生殖系中表观遗传修饰的机制。体细胞核的甲基化发生了显著变化，导致一些印记基因和非印记基因的去甲基化。这些表观遗传修饰是可遗传的，并通过体细胞核中Peg 1/Mest印记基因的沉默母系等位基因的重新激活来判断其影响基因表达。体细胞核表观基因型的这种显著变化与观察到的EG-体细胞杂种细胞的多能性一致，因为它们在嵌合体胚胎中分化成各种组织。在体外EG-体细胞杂交体中观察到的表观遗传修饰与生殖细胞发育期间发生的重编程事件相当。
Genomic reprogramming of primordial germ cells (PGCs), which includes genome-wide demethylation, prevents aberrant epigenetic modifications from being transmitted to subsequent generations, This process also ensures that homologous chromosomes first acquire an identical epigenetic status before an appropriate switch in the imprintable loci in the female and male germ lines. Embryonic germ (EG) cells have a similar epigenotype to PGCs from which they are derived, We used EG cells to investigate the mechanism of epigenetic modifications in the germ line by analysing the effects on a somatic nucleus in the EG-thymic lymphocyte hybrid cells. There were striking changes in methylation of the somatic nucleus, resulting in demethylation of several imprinted and non-imprinted genes, These epigenetic modifications were heritable and affected gene expression as judged by re-activation of the silent maternal allele of Peg1/Mest imprinted gene in the somatic nucleus. This remarkable change in the epigenotype of the somatic nucleus is consistent with the observed pluripotency of the EG-somatic hybrid cells as they differentiated into a variety of tissues in chimeric embryos. The epigenetic modifications observed in EG-somatic cell hybrids in vitro are comparable to the reprogramming events that occur during germ cell development.