Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain
Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain
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DOI：
10.1073/pnas.1100314108
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发表时间：
2011-03-08
影响因子：
11.1
通讯作者：
Forbes-Lorman, Robin M.
中科院分区：
文献类型：
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作者：
Auger, Catherine J.;Coss, Dylan;Forbes-Lorman, Robin M.
虽然在发育中的大脑中类固醇激素暴露会改变一些DNA甲基化模式，但对类固醇激素水平的变化如何影响成人大脑中的DNA甲基化模式知之甚少。类固醇激素在成年人的大脑中起调节基因表达的作用。具体而言，表达的社会相关肽加压素（AVP）内的床核的终纹（BST）的成人大脑是依赖于睾酮暴露。去势显著降低BST内AVP表达，睾酮替代恢复BST内AVP表达。由于mRNA表达的减少与DNA启动子甲基化的增加相关，我们探讨了AVP在成人大脑中的表达是通过AVP基因启动子的持续表观遗传修饰来维持的假设。我们发现，成年雄性大鼠去势导致AVP mRNA表达减少，BST中AVP启动子内特定CpG位点甲基化增加。同样，去势显著增加雌激素受体α（ER α）mRNA的表达和减少ER α启动子甲基化的BST。这些变化被睾酮替代所阻止。这表明，成人大脑中某些类固醇反应基因的DNA启动子甲基化状态是通过循环类固醇激素的存在而积极维持的。类固醇激素的存在下，在成人大脑中某些基因的甲基化或去甲基化状态的维持可能在行为相关系统的稳态调节中发挥作用。
Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor a (ER alpha) mRNA expression and decreased ERa promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems.