A differentially methylated single CpG-site is correlated with estrogen receptor alpha transcription
A differentially methylated single CpG-site is correlated with estrogen receptor alpha transcription
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DOI：
10.1016/j.jsbmb.2012.01.009
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发表时间：
2012-05-01
影响因子：
4.1
通讯作者：
Ulbrich, Susanne E.
中科院分区：
文献类型：
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作者：
Fuerst, Rainer W.;Kliem, Heike;Ulbrich, Susanne E.
雌激素受体α (ESR1) 启动子区域的 DNA 甲基化被认为是调节其 mRNA 丰度的表观遗传机制。我们质疑雄性生长仔猪的组织在 DNA 甲基化方面是否受到发育过程中不同血浆雌二醇 17 β (E2) 浓度的影响。此外，我们的目的是扩大目前对生理环境中 ESR1 表观遗传调控的有限理解。使用甲基化敏感的高分辨率熔解 (MS-HRM) 和焦磷酸测序相结合，对 ESR1 的三个不同遗传区域进行了分析。出乎意料的是，主要的 E2 浓度差异仅与 DNA 甲基化和 mRNA 丰度的微小变化有轻微相关。然而，通过分析转录本丰度差异最大的两个组织，我们能够在心脏和附睾之间的 ESR1 +1 kb 基因内区域中发现一个显着不同甲基化的 CpG 位点。有趣的是，这个单一的 CpG 位点被确定为转录阻遏物 TG 相互作用因子 1 (TGIF) 的假定结合位点，它可以招募组蛋白脱乙酰酶 1 (HDAC1)，从而导致染色质浓缩。事实上，染色质免疫沉淀证实，在 DNA 甲基化较高的情况下，特定 ESR1 位置处的组蛋白 H3 存在减少。因此，我们假设 ESR1 表达可能表现为基于单 CpG 位点的甲基化差异损害转录因子结合。 (C) 2012 Elsevier Ltd. 保留所有权利。
DNA methylation of the promoter region of estrogen receptor alpha (ESR1) is recognized as an epigenetic mechanism that regulates its mRNA abundance. We questioned whether tissues in male growing piglets were influenced in terms of DNA methylation by the developmentally occurring distinct plasma estradiol-17 beta (E2) concentrations. Additionally, we aimed at broadening the currently limited understanding of the epigenetic regulation of ESR1 in physiological settings. Three distinct genetic regions of ESR1 were analyzed using a combination of methylation-sensitive high resolution melting (MS-HRM) and pyrosequencing. Unexpectedly, major E2 concentration differences were only marginally associated with minor variations in DNA methylation and mRNA abundance. However, by analyzing two tissues showing the greatest differences in transcript abundance, we were able to find one single CpG site in the +1 kb intragenic region of ESR1 strikingly differently methylated between heart vs. epididymis. Interestingly, this single CpG-site was identified as a putative binding site for the transcriptional repressor TG-interacting factor 1 (TGIF) which can recruit histone deacetylase 1 (HDAC1) leading to chromatin condensation. Indeed, chromatin immunoprecipitation confirmed a reduced histone H3 presence at the specific ESR1 location in case of higher DNA methylation. We therefore hypothesize that ESR1 expression may be manifested by a single-CpG-site based methylation difference impairing transcription factor binding. (C) 2012 Elsevier Ltd. All rights reserved.