Epigenomics, 2015, 5(1):51-63.

Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or anti‑HDAC in breast cancer cell lines

Aslihan Dagdemir, Julie Durif, Marjolaine Ngollo, et al

Centre Jean Perrin, Département d'Oncogénétique, CBRV, Clermont-Ferrand, France

AIM:

The isoflavones genistein, daidzein and equol (daidzein metabolite) have been reported to interact with epigenetic modifications, specifically hypermethylation of tumor suppressor genes. The objective of this study was to analyze and understand the mechanisms by which phytoestrogens act on chromatin in breast cancer cell lines.

MATERIALS & METHODS:

Two breast cancer cell lines, MCF-7 and MDA-MB 231, were treated with genistein (18.5 µM), daidzein (78.5 µM), equol (12.8 µM), 17β-estradiol (10 nM) and suberoylanilide hydroxamic acid (1 µM) for 48 h. A control with untreated cells was performed. 17β-estradiol and an anti-HDAC were used to compare their actions with phytoestrogens. The chromatin immunoprecipitation coupled with quantitative PCR was used to follow soy phytoestrogen effects on H3 and H4 histones on H3K27me3, H3K9me3, H3K4me3, H4K8ac and H3K4ac marks, and we selected six genes (EZH2, BRCA1, ERα, ERβ, SRC3 and P300) for analysis.

RESULTS:

Soy phytoestrogens induced a decrease in trimethylated marks and an increase in acetylating marks studied at six selected genes.

CONCLUSION:

We demonstrated that soy phytoestrogens tend to modify transcription through the demethylation and acetylation of histones in breast cancer cell lines.

英国《表观基因学》，2013年2月

在乳腺癌细胞中组蛋白赖氨酸三甲基化或乙酰化可以被植物雌激素，雌激素或 抗‑HDAC 调节

阿斯勒汗 达代米尔，朱莉 杜立夫，马郁兰 恩戈洛，等

法国克莱蒙费朗让 · 佩林中心遗传学科

目的︰

异黄酮金雀异黄素、 大豆苷元和雌马酚 （大豆黄酮代谢物）被报道与表观遗传改性相互作用，特别是肿瘤抑癌基因的甲基化。本研究的目的是分析和了解植物雌激素对乳腺癌细胞中的染色质的活性机制。

材料与方法︰

两种乳腺癌细胞，MCF-7 和 MDA-MB-231，被金雀异黄素 (18.5 µ M)，大豆黄酮 (78.5 µ M)，雌马酚 (12.8 µ M)，17β- 雌二醇 (10 nM) 和肟异羟肟酸 (1 µM) 处理 48 小时。与未经处理的细胞进行对照。17β-雌二醇和抗 HDAC 被用来与植物雌激素的活性比较。染色质免疫沉淀加上荧光定量 PCR 被用来跟踪大豆植物雌激素对 H3 和 H4 组蛋白，对 H3K27me3、 H3K9me3、 H3K4me3、 H4K8ac 和 H3K4ac 标记的影响，并且我们选择了六个基因 （EZH2，BRCA1、 e α、 e β、 SRC3 和 P300） 进行分析。

结果︰

大豆植物雌激素在所选的6个基因中诱导三甲基化标记物减少和增加乙酰化标记产物。

结论︰

我们证明了大豆植物雌激素倾向于通过在乳腺癌细胞中组蛋白的去甲基化和乙酰化修改转录。