A transcriptional insulator at the imprinted H19/Igf2 locus.
A transcriptional insulator at the imprinted H19/Igf2 locus.
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DOI：
10.1101/gad.14.15.1908
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发表时间：
2000-08
影响因子：
10.5
通讯作者：
C. R. Kaffer;M. Srivastava;K. Park;E. Ives;S. Hsieh;J. Batlle;A. Grinberg;S. Huang;K. Pfeifer
中科院分区：
文献类型：
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作者：
C. R. Kaffer;M. Srivastava;K. Park;E. Ives;S. Hsieh;J. Batlle;A. Grinberg;S. Huang;K. Pfeifer
Igf2和H19表现出亲本来源特异性单等位基因表达。H19由母本染色体表达，Igf2由父本染色体表达。这两个基因共享增强子元件，并且两个基因的单等位基因表达依赖于H19启动子上游的顺式作用序列。在这项工作中，我们研究的机制，该区域沉默的母亲Igf2等位基因，我们证明，删除该区域可以导致高水平的激活H19和Igf2从一个单一的染色体。此外，通过在异源位置的启动子和其增强子之间插入该顺式元件，我们证明了该序列携带绝缘子活性和被稳定印迹的能力。我们还在体外的绝缘子的特点，并表明它既不是增强子，也不是启动子特异性。
Igf2 and H19 exhibit parent-of-origin-specific monoallelic expression. H19 is expressed from the maternal chromosome and Igf2 from the paternal. The two genes share enhancer elements and monoallelic expression of both genes is dependent on cis-acting sequences upstream of the H19 promoter. In this work we examine the mechanisms by which this region silences the maternal Igf2 allele and we demonstrate that deletion of this region can result in high levels of activation of both H19 and Igf2 from a single chromosome. Moreover, by inserting this cis element between a promoter and its enhancer at a heterologous position, we demonstrate that the sequences carry both insulator activity and the ability to be stably imprinted. We also characterize the insulator in vitro and show that it is neither enhancer nor promoter specific.