C. Murgatroyd: School of Healthcare Science, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK.
Exp Physiol. 2014 Jan;99(1):62-5. doi: 10.1113/expphysiol.2013.076141. Epub 2013 Sep 13.
Arginine vasopressin plays a pivotal role in the control of long-lasting effects of early-life stress on the brain. We previously reported that maternal separation in mice persistently upregulates Avp gene expression associated with reduced DNA methylation of a region in the Avp enhancer. This early-life stress-responsive region serves as a binding site for the methyl-CpG binding protein 2, which in turn is controlled through neuronal activity. We also found that the ability of methyl-CpG binding protein 2 to regulate transcription of the Avp gene and induce DNA methylation occurred through the recruitment of components of the epigenetic machinery. Understanding the sequential events involved in the epigenetic regulation of a gene should allow for targeted approaches aimed at reprogramming expression during development and possibly later life.
精氨酸加压素在控制早期生活压力对大脑的持久影响方面起着关键作用。我们之前的研究表明，在小鼠中进行的母婴分离会持续上调与 Avp 增强子中一个区域的 DNA 甲基化减少相关的 Avp 基因表达。这个早期生活压力反应性区域是甲基化CpG 结合蛋白 2 的结合位点，而后者又受到神经元活性的控制。我们还发现，甲基化CpG 结合蛋白 2 调节 Avp 基因转录和诱导 DNA 甲基化的能力是通过招募表观遗传机制的成分来实现的。了解基因表观遗传调控中涉及的顺序事件，应该可以为在发育过程中甚至以后的生活中重新编程表达的靶向方法提供依据。
