Jones B K, Levorse J M, Tilghman S M
Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544 USA.
Genes Dev. 1998 Jul 15;12(14):2200-7. doi: 10.1101/gad.12.14.2200.
Three models have been proposed to explain the imprinting of the mouse Igf2 gene on the maternal chromosome. We ruled out the importance of DNA methylation at Igf2 by showing that silencing of Igf2 accompanying the loss of DNA methylation could be overcome by a mutation at the neighboring H19 gene that activates Igf2. By replacing the H19 structural gene with a protein-coding gene, we have ruled out a role for H19 RNA in the imprinting of Igf2. This replacement resulted in sporadic activation of the H19 promoter on the paternal chromosome without affecting the level of expression of Igf2, a finding that is inconsistent with strict promoter competition between the genes. We conclude that a transcriptional model involving access to a common set of enhancers shared between Igf2 and H19 is the most likely explanation for Igf2 imprinting.
已经提出了三种模型来解释小鼠Igf2基因在母源染色体上的印记。我们通过实验排除了DNA甲基化在Igf2印记中的重要性，实验表明，伴随DNA甲基化缺失的Igf2沉默可被邻近的H19基因的突变所克服，该突变激活了Igf2。通过用蛋白质编码基因取代H19结构基因，我们排除了H19 RNA在Igf2印记中的作用。这种取代导致父源染色体上H19启动子的散在激活，而不影响Igf2的表达水平，这一发现与基因之间严格的启动子竞争不一致。我们得出结论，涉及共享一组Igf2和H19之间的增强子的转录模型是Igf2印记最可能的解释。
