Telomeric transgenes are silenced in adult mouse tissues and embryo fibroblasts but are expressed in embryonic stem cells
Telomeric transgenes are silenced in adult mouse tissues and embryo fibroblasts but are expressed in embryonic stem cells
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DOI：
10.1634/stemcells.2007-0478
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发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Murnane, John P.
中科院分区：
文献类型：
--
作者：
Gao, Qing;Reynolds, Gloria E.;Murnane, John P.
除了保护染色体末端的作用外，端粒还影响相邻基因的表达，这一过程称为端粒位置效应。我们先前报道了位于小鼠胚胎干细胞端粒附近的neo和HSV-tk转基因最初以低水平表达，然后通过涉及DNA甲基化的过程在培养中逐渐沉默。我们还报道了从这些胚胎干细胞克隆之一产生的小鼠中分离的三种不同组织中这些端粒转基因的广泛DNA甲基化。在本研究中，我们证明了从两种不同的小鼠品系中分离的胚胎成纤维细胞显示出广泛的DNA甲基化和端粒转基因沉默。与此观察结果一致，我们还证明了很少或没有检测到的表达HSV-tk端粒转基因在体细胞组织中使用全身成像。相反，这两种端粒转基因在从这些相同的小鼠品系分离的胚胎干细胞系中以低水平表达并且具有很少的DNA甲基化。我们的研究结果表明，哺乳动物细胞中的端粒位置效应可以被观察到，无论是在植入前胚胎的胚胎干细胞中的低水平表达，还是在分化的细胞和体细胞组织中的完全沉默和DNA甲基化。端粒转基因的这种表达模式表明，亚端粒区域，像大部分的基因组，在植入前胚胎，一个过程，已被提出是重要的早期胚胎发育的表观遗传重编程。
In addition to their role in protecting the ends of chromosomes, telomeres also influence the expression of adjacent genes, a process called telomere-position effect. We previously reported that the neo and HSV-tk transgenes located adjacent to telomeres in mouse embryonic stem cells are initially expressed at low levels and then become gradually silenced upon passage in culture through a process involving DNA methylation. We also reported extensive DNA methylation in these telomeric transgenes in three different tissues isolated from mice generated from one of these embryonic stem cell clones. In the present study, we demonstrate that embryo fibroblasts isolated from two different mouse strains show extensive DNA methylation and silencing of the telomeric transgenes. Consistent with this observation, we also demonstrate little or no detectable expression of the HSV-tk telomeric transgene in somatic tissues using whole body imaging. In contrast, both telomeric transgenes are expressed at low levels and have little DNA methylation in embryonic stem cell lines isolated from these same mouse strains. Our results demonstrate that telomere-position effect in mammalian cells can be observed either as a low level of expression in embryonic stem cells in the preimplantation embryo or as complete silencing and DNA methylation in differentiated cells and somatic tissues. This pattern of expression of the telomeric transgenes demonstrates that subtelomeric regions, like much of the genome, are epigenetically reprogrammed in the preimplantation embryo, a process that has been proposed to be important in early embryonic development.