Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan, Germany.
Mol Cell Endocrinol. 2012 Jan 2;348(1):67-77. doi: 10.1016/j.mce.2011.07.032. Epub 2011 Jul 23.
Epigenetic events controlling the transcriptional regulation of genes involved in endometrial function during the estrous cycle and early pregnancy have only sparsely been investigated. We analyzed the gene expression of DNA methyltransferases and the most prominent endocrine transcriptional mediator estrogen receptor alpha (ESR1) in the bovine endometrium of heifers at 0, 12 and 18 days following estrous and at day 18 after insemination. The luminometric methylation assay for the investigation of global DNA methylation and an elegant combination of methylation-sensitive high resolution melting and pyrosequencing for local methylation levels of ESR1 were deployed. In spite of differential gene expression of ESR1 among groups, no differences in endometrial ESR1 DNA methylation during neither estrous cycle nor early pregnancy were determined. Global DNA methylation prevailed at similar low levels in endometrium, likely controlled by the observed moderate DNMT3b expression. Thus, the epigenetic contribution of DNA methylation influencing endometrial function seems rather limited. However, because a control tissue expressing only minute amounts of ESR1 transcripts was locally significantly higher methylated, DNA methylation might contribute to an appropriate tissue-specific expression status underlying further specific control mechanisms of gene transcription.
在发情周期和早期妊娠期间,控制参与子宫内膜功能的基因转录调控的表观遗传事件仅得到了稀疏的研究。我们分析了牛发情后 0、12 和 18 天以及授精后 18 天的小母牛子宫内膜中 DNA 甲基转移酶和最突出的内分泌转录调节剂雌激素受体 α(ESR1)的基因表达。我们采用了用于研究全局 DNA 甲基化的发光甲基化测定法,以及用于 ESR1 局部甲基化水平的甲基敏感高分辨率融解和焦磷酸测序的巧妙组合。尽管 ESR1 在不同组之间的基因表达存在差异,但在发情周期和早期妊娠期间,子宫内膜 ESR1 DNA 甲基化没有差异。子宫内膜中普遍存在类似的低水平的全局 DNA 甲基化,可能由观察到的中度 DNMT3b 表达控制。因此,影响子宫内膜功能的 DNA 甲基化的表观遗传贡献似乎相当有限。然而,由于表达 ESR1 转录本的量很少的对照组织局部甲基化程度显著更高,因此 DNA 甲基化可能有助于特定控制机制下基因转录的适当组织特异性表达状态。