Aberrant DNA methylation suppresses expression of estrogen receptor 1 (ESR1) in ovarian endometrioma
Aberrant DNA methylation suppresses expression of estrogen receptor 1 (ESR1) in ovarian endometrioma
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DOI：
10.1186/s13048-019-0489-1
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发表时间：
2019-02-06
影响因子：
4
通讯作者：
Sugino, Norihiro
中科院分区：
文献类型：
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作者：
Maekawa, Ryo;Mihara, Yumiko;Sugino, Norihiro
在卵巢子宫内膜瘤（OE）中，各种类固醇激素受体的表达状态与异位子宫内膜（EE）中的表达状态相比发生了改变。例如，在OE中，编码ER α的雌激素受体1 （estrogen receptor 1, ESR1）和孕激素受体（progesterone receptor， PGR）表达下调，而编码ER β的ESR2表达上调。这些变化的原因尚不清楚。基因特定区域的DNA甲基化可导致组织特异性基因表达。这些区域被称为组织依赖性和差异甲基化区域（T-DMRs）。我们之前报道了正常组织中ESR1的组织特异性表达受T-DMR的DNA甲基化调节。在本研究中，我们研究了T-DMR的异常DNA甲基化是否与OE中ESR1、ESR2和PGR的表达改变有关。采用定量RT-PCR检测ESR1、ESR2和PGR基因表达水平。OE组ESR1和PGR表达量显著低于EE组，ESR2表达量显著高于EE组。使用Infinium HumanMethylation450K BeadChip和亚硫酸钠测序检测DNA甲基化状态。OE组ESR1的T-DMRs DNA甲基化显著高于EE组，但ESR2和PGR的DNA甲基化状态无显著差异。在OE中，T-DMR的异常DNA甲基化与ESR1的表达受损有关，但与ESR2和PGR的表达改变无关。
In ovarian endometriomas (OE), the expression statuses of various steroid hormone receptors are altered compared with their expression statuses in eutopic endometrium (EE). For example, in OE, the expressions of estrogen receptor 1 (ESR1), which encodes ER alpha, and progesterone receptor (PGR) are downregulated, while the expression of ESR2, which encodes ER beta, is upregulated. The causes of these changes are unclear. DNA methylation of a specific region of a gene can result in tissue-specific gene expression. Such regions are called tissue-dependent and differentially methylated regions (T-DMRs). We previously reported that the tissue-specific expression of ESR1 is regulated by DNA methylation of a T-DMR in normal tissues. In the present study, we examined whether aberrant DNA methylation of the T-DMR is associated with the altered expressions of ESR1, ESR2 and PGR in OE.Gene expression levels of ESR1, ESR2 and PGR were measured by quantitative RT-PCR. The expression levels of ESR1 and PGR were significantly lower and the expression level of ESR2 was significantly higher in OE than in EE. DNA methylation statuses were examined with an Infinium HumanMethylation450K BeadChip and sodium bisulfite sequencing. DNA methylation at the T-DMRs of ESR1 were significantly higher in OE than in EE, but no significant differences were observed in the DNA methylation statuses of ESR2 and PGR.Aberrant DNA methylation of the T-DMR was associated with the impaired expression of ESR1, but not the altered expressions of ESR2 and PGR, in OE.