Genistein alters methylation patterns in mice
Genistein alters methylation patterns in mice
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DOI：
10.1093/jn/132.8.2419s
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发表时间：
2002-08-01
影响因子：
4.2
通讯作者：
Lubahn, DB
中科院分区：
文献类型：
--
作者：
Day, JK;Bauer, AM;Lubahn, DB
在这项研究中，我们研究了植物雌激素金雀异黄素对DNA甲基化的影响。DNA甲基化被认为通过调节染色质结构的变化来抑制基因的转录。据报道，在少数研究中，雌激素类化合物可以调节DNA甲基化。此外，植物雌激素被认为影响一些人类疾病的进展，如雌激素依赖型癌症、骨质疏松症和心血管疾病。具体地说，我们的工作假设是，某些大豆植物雌激素，如染料木素，可能通过保持保护性的DNA甲基化特征而参与预防某些前列腺癌和乳腺癌的发展。本研究的目的是使用小鼠差异甲基化杂交(DMH)阵列来检测小鼠基因组中胞嘧啶鸟嘌呤二核苷酸(CpG)岛的甲基化状态的变化，方法是检测金雀异黄素对这些甲基化模式的影响。以酪蛋白为基础的饲料(对照组)或含染料木素300 mg/kg的饲料按4种方案喂养雄性小鼠：对照组饲料4wk，染料木素饲料4wk，对照饲料2wk，染料木素饲料2wk，染料木素饲料2wk，对照饲料2wk。然后用DMH阵列对肝、脑和前列腺的DNA进行筛选。对甲基化差异的克隆进行测序，并与已知序列进行比较。总之，金雀异黄素饮食的摄入量与小鼠特定基因CpG岛上前列腺DNA甲基化的变化呈正相关。
In this study we examine the effect of the phytoestrogen genistein on DNA methylation. DNA methylation is thought to inhibit transcription of genes by regulating alterations in chromatin structure. Estrogenic compounds have been reported to regulate DNA methylation in a small number of studies. Additionally, phytoestrogens are believed to affect progression of some human diseases, such as estrogen-dependent cancers, osteoporosis and cardiovascular disease. Specifically, our working hypothesis is that certain soy phytoestrogens, such as genistein, may be involved in preventing the development of certain prostate and mammary cancers by maintaining a protective DNA methylation profile. The objective of the present study is to use mouse differential methylation hybridization (DMH) arrays to test for changes in the methylation status of the cytosine guanine dinucleotide (CpG) islands in the mouse genome by examining how these methylation patterns are affected by genistein. Male mice were fed a casein-based diet (control) or the same diet containing 300 mg genistein/kg according to one of four regimens: control diet for 4 wk, genistein diet for 4 wk, control diet for 2 wk followed by genistein diet for 2 wk and genistein diet for 2 wk followed by control diet for 2 wk. DNA from liver, brain and prostate were then screened with DMH arrays. Clones with methylation differences were sequenced and compared with known sequences. In conclusion, consumption of genistein diet was positively correlated with changes in prostate DNA methylation at CpG islands of specific mouse genes.