Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells
Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells
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金雀异黄素促进子宫内膜基质细胞中类固醇生成因子 1 (SF-1) 启动子的 DNA 去甲基化
DOI：
10.1016/j.bbrc.2011.07.104
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Matsukura H
中科院分区：
文献类型：
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作者：
Isagawa T;Nagae G;Shiraki N;Fujita T;Sato N;Ishikawa S;Kume S;Aburatani H;Matsukura H
最近研究表明，染料木素(Genistein，GEN)是一种豆制品中的植物雌激素，在多种细胞中是一种表观遗传调节剂，但其对子宫内膜的影响尚未确定。我们研究了Gen在体内和体外对小鼠子宫细胞的影响。口服GEN 1周可诱导去卵巢(OVX)小鼠子宫内膜轻度增殖，同时伴有类固醇生成因子1(SF-1)基因表达的诱导。Gen诱导SF-1启动子中多个CpG位点去甲基化；这些位点广泛甲基化，因此在正常子宫内膜中沉默。基因介导的启动子去甲基化主要发生在子宫腔侧，而不是肌层侧，这表明表观遗传学变化主要表现在再生细胞中。用高分辨熔融法(HRM)筛选子宫内膜间质细胞原代培养细胞克隆，以检测基因介导的DNA甲基化改变。每20个集落形成细胞克隆中就有一个显示出Gen诱导的SF-1去甲基化。通过多次连续克隆，该克隆具有较高的增殖能力和持续的集落形成活性。我们认为只有一部分子宫内膜细胞能够接受基因的表观遗传调控。
It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.