Sex- and tissue-specific expression of maintenance and de novo DNA methyltransferases upon low dose X-irradiation in mice
Sex- and tissue-specific expression of maintenance and de novo DNA methyltransferases upon low dose X-irradiation in mice
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DOI：
10.1016/j.bbrc.2004.10.002
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发表时间：
2004-12-03
影响因子：
3.1
通讯作者：
Kovalchuk, O
中科院分区：
文献类型：
--
作者：
Raiche, J;Rodriguez-Juarez, R;Kovalchuk, O
DNA甲基化对于给定生物体的正常发育、增殖和基因组稳定性的适当维持至关重要。已知影响基因组稳定性的各种DNA损伤剂也显示出改变DNA甲基化模式。我们最近在辐射对DNA甲基化影响的研究领域开创了先河，发现辐射暴露导致大量的剂量依赖性和组织特异性DNA低甲基化，这在雌性动物的脾脏和肝脏中更为明显。辐射诱导的DNA低甲基化的确切机制仍有待揭示。我们之前已经表明，其中一种机制可能与DNA修复有关。另一种可能的机制可能与DNA甲基转移酶（DNMT）表达的变化有关。在目前的研究中，我们研究了辐射诱导的表达的变化，维持DNMT1，和从头甲基转移酶DNMT3a和DNMT3b在脾脏和肝脏的辐射动物。这是由急性和慢性IR诱导的完整动物的脾脏和肝脏中的甲基化变化的研究，以及在改变性激素状态的动物证实。在这里，我们报告，辐射诱导的DNA甲基化的变化与辐射诱导的DNA甲基转移酶的表达变化。我们提出的数据在辐射诱导的DNA甲基转移酶的表达的组织特异性，并证明，从头甲基转移酶DNMT3a和DNMT3b的表达的变化是最重要的辐射诱导的DNA甲基化的改变。我们还讨论了性激素，特别是雌激素，在性别特异性辐射诱导的甲基化变化的产生中的作用。(C)2004爱思唯尔公司All rights reserved.
DNA methylation is crucial for normal development, proliferation, and proper maintenance of genome stability for a given organism. A variety of DNA damaging agents that are known to affect genome stability were also shown to alter DNA methylation patterns. We have recently pioneered the studies in the area of the radiation effects on DNA methylation, and found that radiation exposure led to substantial dose-dependent and tissue-specific DNA hypomethylation, which was much more pronounced in spleen and liver of female animals. The exact mechanisms of radiation-induced DNA hypomethylation are still to be uncovered. We have previously shown that one of those mechanisms may potentially be DNA repair related. Another possible mechanism may be linked to changes in the expression of DNA methyltransferases (DNMTs). In the current study, we examined the radiation-induced changes in expression of maintenance DNMT1, and de novo methyltransferases DNMT3a and DNMT3b in spleen and liver of irradiated animals. This was paralleled by the studies of acute and chronic IR-induced methylation changes in spleen and liver of intact animals, as well as in animals with altered sex hormone status. Here we report that radiation-induced DNA methylation changes correlated with radiation-induced alterations in expression of DNA methyltransferases. We present the data on tissue-specificity in radiation-induced expression of DNA methyltransferases, and prove that changes in the expression of de novo methyltransferases DNMT3a and DNMT3b are the most important in radiation-induced DNA methylation alterations. We also discuss the role of sex hormones, especially estrogen, in the generation of the sex-specific radiation-induced methylation changes. (C) 2004 Elsevier Inc. All rights reserved.