Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression.
Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression.
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DOI：
10.1186/s13148-021-01017-5
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发表时间：
2021-01-30
影响因子：
5.7
通讯作者：
Connelly JJ
中科院分区：
文献类型：
--
作者：
Danoff JS;Wroblewski KL;Graves AJ;Quinn GC;Perkeybile AM;Kenkel WM;Lillard TS;Parikh HI;Golino HF;Gregory SG;Carter CS;Bales KL;Connelly JJ
神经肽催产素调节哺乳动物的社会行为。催产素信号的中断是许多精神病理学的特征。催产素参与精神疾病的一个常用生物标志物是催产素受体基因（OXTR）的DNA甲基化。这些研究集中在OXTR的两个区域中的DNA甲基化，外显子3和与外显子1和内含子1重叠的称为MT2的区域。然而，外显子3和MT2在调节脑中OXTR基因表达中的相对贡献目前尚不清楚。在这里，我们使用草原田鼠作为翻译的动物模型，以调查遗传，表观遗传和环境因素影响Oxtr基因表达的大脑区域，已被证明是驱动Oxtr相关的行为在田鼠，神经核。我们表明，在草原田鼠的OXTR的遗传结构类似于人类OXTR。然后，我们研究了早期生活经历对Oxtr启动子周围CpG岛的两个区域（MT 2和外显子3）DNA甲基化的影响。我们发现，早期培养的形式，父母的照顾，结果在MT2和外显子3的DNA低甲基化的Oxtr，但只有MT2的DNA甲基化与Oxtr基因的表达。网络分析表明MT2 3′端的CpG位点与Oxtr基因表达的相关性最高。我们还确定了两个新的SNPs的外显子3的Oxtr在草原田鼠和一个新的替代转录起源于第三内含子的基因。新的替代转录本的表达与SNP KLW2的基因型相关。这些结果确定了假定的监管功能的OXTR在草原田鼠，通知未来的研究OXTR在人类社会行为和障碍。这些研究表明，在草原田鼠中，MT2的DNA甲基化，特别是在3′部分，比外显子3的DNA甲基化更能预测Oxtr基因的表达。类似地，在人类颞叶皮层中，我们发现MT2 3′端的DNA甲基化与OXTR表达相关。总之，这些结果表明，在所研究的CpG位点中，MT2的DNA甲基化可能是OXTR基因表达的最可靠指标。我们还确定了草原田鼠OXTR，包括单核苷酸多态性和替代转录，进一步发展的草原田鼠作为OXTR研究的翻译模型的新功能。
The neuropeptide oxytocin regulates mammalian social behavior. Disruptions in oxytocin signaling are a feature of many psychopathologies. One commonly studied biomarker for oxytocin involvement in psychiatric diseases is DNA methylation at the oxytocin receptor gene (OXTR). Such studies focus on DNA methylation in two regions of OXTR, exon 3 and a region termed MT2 which overlaps exon 1 and intron 1. However, the relative contribution of exon 3 and MT2 in regulating OXTR gene expression in the brain is currently unknown. Here, we use the prairie vole as a translational animal model to investigate genetic, epigenetic, and environmental factors affecting Oxtr gene expression in a region of the brain that has been shown to drive Oxtr related behavior in the vole, the nucleus accumbens. We show that the genetic structure of Oxtr in prairie voles resembles human OXTR. We then studied the effects of early life experience on DNA methylation in two regions of a CpG island surrounding the Oxtr promoter: MT2 and exon 3. We show that early nurture in the form of parental care results in DNA hypomethylation of Oxtr in both MT2 and exon 3, but only DNA methylation in MT2 is associated with Oxtr gene expression. Network analyses indicate that CpG sites in the 3′ portion of MT2 are most highly associated with Oxtr gene expression. We also identify two novel SNPs in exon 3 of Oxtr in prairie voles and a novel alternative transcript originating from the third intron of the gene. Expression of the novel alternative transcript is associated with genotype at SNP KLW2. These results identify putative regulatory features of Oxtr in prairie voles which inform future studies examining OXTR in human social behaviors and disorders. These studies indicate that in prairie voles, DNA methylation in MT2, particularly in the 3′ portion, is more predictive of Oxtr gene expression than DNA methylation in exon 3. Similarly, in human temporal cortex, we find that DNA methylation in the 3′ portion of MT2 is associated with OXTR expression. Together, these results suggest that among the CpG sites studied, DNA methylation of MT2 may be the most reliable indicator of OXTR gene expression. We also identify novel features of prairie vole Oxtr, including SNPs and an alternative transcript, which further develop the prairie vole as a translational model for studies of OXTR.
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DOI：
10.1016/j.ijpsycho.2018.01.008
发表时间：
2019-03
期刊：
International journal of psychophysiology : official journal of the International Organization of Psychophysiology
影响因子：
--
作者：
Ebner NC;Lin T;Muradoglu M;Weir DH;Plasencia GM;Lillard TS;Pournajafi-Nazarloo H;Cohen RA;Sue Carter C;Connelly JJ
通讯作者：
Connelly JJ
影响因子：
3.7
作者：
Chagnon YC;Potvin O;Hudon C;Préville M
通讯作者：
Préville M
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
11
作者：
Cecil, C. A. M.;Lysenko, L. J.;Jaffee, S. R.;Pingault, J-B;Smith, R. G.;Relton, C. L.;Woodward, G.;McArdle, W.;Mill, J.;Barker, E. D.
通讯作者：
Barker, E. D.
影响因子：
3.7
作者：
Golino, Hudson F.;Epskamp, Sacha
通讯作者：
Epskamp, Sacha