The glucocorticoid receptor gene exon 1-F promoter is not methylated at the NGFI-A binding site in human hippocampus
The glucocorticoid receptor gene exon 1-F promoter is not methylated at the NGFI-A binding site in human hippocampus
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DOI：
10.1080/15622970701429862
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Meyer, Jobst
中科院分区：
文献类型：
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作者：
Moser, Dirk;Molitor, Anne;Meyer, Jobst
最近的研究表明，早期的生活经历，如母亲护理的变化，可以对褐家鼠的生理和内分泌应激反应产生深远的影响。低孕产期护理导致位于海马糖皮质激素受体基因外显子1(7)启动子的神经生长因子诱导蛋白A(NGFI-A，Egr1)结合位点甲基化增加，导致NR3C1表达降低，从而降低糖皮质激素介导的负反馈对下丘脑-垂体肾上腺轴活动的影响。人类糖皮质激素受体基因(NR3C1)与大鼠相比具有高度相似的5‘结构，人类替代外显子1-F是大鼠外显子1(7)的同源基因。基于大鼠的证据和调控序列的高度同源性，我们检测了死后海马组织中人糖皮质激素受体外显子I-F特异性启动子中相应的NGFI-A结合位点的甲基化模式。与大鼠的研究结果相反，在32名受试者中，NGFI-A结合位点内的两个CpG基序都没有甲基化。这些观察可能反映了人类和大鼠不同的启动子甲基化模式。
Recent research has demonstrated that early life experience, such as variation in maternal care, can have a profound impact on the physiological and endocrine stress response of Rattus norvegicus. Low maternal care resulted in increased methylation of the nerve growth factor-inducible protein A (NGFI-A, EGR1) binding site located in the hippocampal glucocorticoid receptor gene (Nr3c1) exon 1(7) promoter, leading to decreased Nr3c1 expression, which results in a reduced efficiency of glucocorticoid-mediated negative feedback on hypothalamus-pituitary adrenal axis activity. The human glucocorticoid receptor gene (NR3C1) has a highly similar 5' structure compared to the rat, and the human alternative exon 1-F is the orthologue to the rat exon 1(7). Based upon the evidence from rats, and the high sequence identity of the regulatory sequences, we examined the methylation pattern of the corresponding NGFI-A binding site in the human glucocorticoid receptor exon I-F specific promoter in post mortem hippocampal tissue. In contrast to the findings in rats, neither of the two CpG motifs within the NGFI-A binding site was methylated in the 32 subjects investigated. These observations might reflect different promoter methylation patterns in humans and rats.