A differentially methylated imprinting control region within the Kcnq1 locus harbors a methylation-sensitive chromatin insulator
A differentially methylated imprinting control region within the Kcnq1 locus harbors a methylation-sensitive chromatin insulator
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DOI：
10.1074/jbc.m200031200
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发表时间：
2002-05-17
影响因子：
4.8
通讯作者：
Ohlsson, R
中科院分区：
文献类型：
--
作者：
Kanduri, C;Fitzpatrick, G;Ohlsson, R
基因组印记现象背后的机制仍然知之甚少。在一个例子中，H19位点上的差异甲基化印迹控制区（ICR）已被证明与甲基化敏感的染色质绝缘子功能有关，该功能显然以亲本来源依赖的方式将邻近的Igf2和H19基因分隔在不同的表达域。然而，目前尚不清楚这种机制是Igf2/H19基因座独有的，还是绝缘子功能是印迹基因调控的共同特征。为了解决这个问题，我们研究了Kcnq1位点上的一个ICR，该ICR调节包括Igf2和H19在内的印迹结构域中父系衍生的p57Kip2和Kcnq1等位基因的远程抑制。我们发现，在中胚层和内胚层起源的体细胞中，这种ICR似乎具有单向染色质绝缘体功能。此外，我们发现CpG甲基化调节了这种绝缘子的功能，这表明甲基化敏感的染色质绝缘子是基因组印迹现象的共同主题。
The mechanisms underlying the phenomenon of genomic imprinting remain poorly understood. In one instance, a differentially methylated imprinting control region (ICR) at the H19 locus has been shown to involve a methylation-sensitive chromatin insulator function that apparently partitions the neighboring Igf2 and H19 genes in different expression domains in a parent of origin-dependent manner. It is not known, however, if this mechanism is unique to the Igf2/H19 locus or if insulator function is a common feature in the regulation of imprinted genes. To address this question, we have studied an ICR in the Kcnq1 locus that regulates long range repression on the paternally derived p57Kip2 and Kcnq1 alleles in an imprinting domain that includes Igf2 and H19. We show that this ICR appears to possess a unidirectional chromatin insulator function in somatic cells of both mesodermal and endodermal origins. Moreover, we document that CpG methylation regulates this insulator function suggesting that a methylation-sensitive chromatin insulator is a common theme in the phenomenon of genomic imprinting.