Imprinting of Igf2 and H19 from a 130 kb YAC transgene.
Imprinting of Igf2 and H19 from a 130 kb YAC transgene.
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来自 130 kb YAC 转基因的 Igf2 和 H19 的印记。
作者：
J. Ainscough;Tsuyoshi Koide;Masako Tada;Sheila C. Barton;M. Surani
印迹控制元件的一个严格测试是检查它们在转基因实验中异位位点的功能。Igf 2和H19是一个更大的印迹区域的一部分，作为第一步，我们研究了这些印迹基因在转基因实验中使用130 kb的YAC克隆。父系遗传后，H19被适当抑制，Igf 2表达，无论拷贝数或遗传背景。母系遗传后，H19一直表达，尽管有一些变异。每拷贝转基因的H19表达水平与Igf 2（-lacZ）顺式表达呈负相关。来自该YAC的H19的一致印记与先前描述的仅发生在多拷贝基因座处的迷你-H19转基因的印记形成对比，其是不一致的，并且倾向于遗传背景效应。我们提出了一个新的模型，其中沉默的H19基因是默认状态和激活后，母系遗传是关键的机械事件在这个地区的印记。此外，Igf 2-lacZ报告基因的原位分析表明，在YAC克隆中存在额外的中胚层特异性增强子。H19过量基因剂量没有检测到明显的表型。
A stringent test for imprint control elements is to examine their function at ectopic loci in transgenic experiments. Igf2 and H19 are part of a larger imprinting region and as a first step, we examined these reciprocally imprinted genes in transgenic experiments using a 130 kb YAC clone. After paternal inheritance, H19 was appropriately repressed and Igf2 was expressed, irrespective of copy number or genetic background. After maternal inheritance H19 was consistently expressed, albeit with some variability. The levels of H19 expression per copy of the transgene inversely correlated with Igf2 (-lacZ) expression in cis. The consistent imprinting of H19 from this YAC contrasts with the previously described imprinting of mini-H19 transgenes, which only occurs at multi-copy loci, is inconsistent, and is prone to genetic background effects. We propose a novel model in which silencing of the H19 gene is the default state and its activation after maternal inheritance is the key mechanistic event for imprinting in this region. In addition, in situ analysis of the Igf2-lacZ reporter indicates that additional mesoderm-specific enhancers are present within the YAC clone. No obvious phenotype was detected from the excess gene dosage of H19.
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DOI：
10.1073/pnas.83.9.2934
发表时间：
1986-05-01
影响因子：
11.1
作者：
PINKEL, D;STRAUME, T;GRAY, JW
通讯作者：
GRAY, JW
影响因子：
10.5
作者：
BRUNKOW, ME;TILGHMAN, SM
通讯作者：
TILGHMAN, SM
转基因小鼠的生产。
影响因子：
--
作者：
Gordon,JW
通讯作者：
Gordon,JW
影响因子：
10.5
作者：
BARTOLOMEI, MS;WEBBER, AL;TILGHMAN, SM
通讯作者：
TILGHMAN, SM
亲代印记：小鼠胰岛素样生长因子 II (Igf2) 基因受抑制的母体等位基因的潜在活性染色质。
影响因子：
10.5
作者：
Sasaki,H;Jones,PA;Chaillet,JR;Ferguson-Smith,AC;Barton,SC;Reik,W;Surani,MA
通讯作者：
Surani,MA