Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.
复制标题
DOI：
10.1038/nn.2270
复制
发表时间：
2009-03
影响因子：
25
通讯作者：
Meaney, Michael J.
中科院分区：
文献类型：
--
作者：
McGowan, Patrick O.;Sasaki, Aya;D'Alessio, Ana C.;Dymov, Sergiy;Labonte, Benoit;Szyf, Moshe;Turecki, Gustavo;Meaney, Michael J.
母亲护理通过糖皮质激素受体表达的表观遗传编程影响大鼠下丘脑-垂体-肾上腺（HPA）功能。在人类中，童年虐待改变了HPA的压力反应，增加了自杀的风险。我们研究了神经元特异性糖皮质激素受体（NR 3C 1）启动子的表观遗传差异之间的死后海马从自杀受害者与儿童虐待的历史，无论是自杀受害者没有儿童虐待或控制。我们发现糖皮质激素受体mRNA水平下降，以及mRNA转录轴承糖皮质激素受体1F剪接变异体和增加胞嘧啶甲基化的NR 3C 1启动子。模仿滥用自杀受害者样本中甲基化状态的补丁甲基化NR 3C 1启动子结构显示NGFI-A转录因子结合和NGFI-A诱导基因转录减少。这些发现将先前的结果从大鼠翻译到人类，并表明父母的照顾对海马糖皮质激素受体表达的表观遗传调控的共同影响。
Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide. We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls. We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A–inducible gene transcription. These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.
登录
查看更多内容
影响因子：
3.7
作者：
Oberlander, Tim F.;Weinberg, Joanne;Devlin, Angela M.
通讯作者：
Devlin, Angela M.
影响因子：
3
作者：
Ernst, Carl;McGowan, Patrick O.;Turecki, Gustavo
通讯作者：
Turecki, Gustavo
影响因子：
--
作者：
Breslin, MB;Geng, CD;Vedeckis, WV
通讯作者：
Vedeckis, WV
影响因子：
14.9
作者：
CLARK, SJ;HARRISON, J;FROMMER, M
通讯作者：
FROMMER, M
DOI：
10.1111/j.1469-7610.1994.tb01284.x
发表时间：
1994-11-01
期刊：
JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES
影响因子：
--
作者：
BIFULCO, A;BROWN, GW;HARRIS, TO
通讯作者：
HARRIS, TO