Global DNA methylation changes spanning puberty are near predicted estrogen-responsive genes and enriched for genes involved in endocrine and immune processes.
Global DNA methylation changes spanning puberty are near predicted estrogen-responsive genes and enriched for genes involved in endocrine and immune processes.
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DOI：
10.1186/s13148-018-0491-2
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发表时间：
2018
影响因子：
5.7
通讯作者：
Ober C
中科院分区：
文献类型：
--
作者：
Thompson EE;Nicodemus-Johnson J;Kim KW;Gern JE;Jackson DJ;Lemanske RF;Ober C
青春期发生的变化与以后生活中对各种疾病的易感性有关，其中许多疾病的特征是患病率的性别特异性差异。遗传和环境因素都与青春期的开始或延迟有关，最近的证据表明表观遗传变化在青春期的开始中也起作用。确定女孩和男孩青春期窗口期出现的整体DNA甲基化变化。使用Infinium 450 K阵列测量全基因组DNA甲基化水平。我们的研究集中在30名女孩和25名男孩青春期前和青春期后（分别为8岁和14岁）的外周血单核细胞（PBMC），其中青春期状态通过坦纳分期证实。我们的研究揭示了347差异甲基化探针（DMPs）的女性和50 DMPs的男性之间的8和14岁（FDR 5%）。女性DMPs位于或接近312个独特的基因中，这些基因由于具有高亲和力的雌激素反应元件而被过度代表（排列P < 2.0 × 10−6），这表明青春期雌激素信号传导的一些影响通过表观遗传机制被修改。对女性青春期DMPs附近的312个基因进行的免疫途径分析（IPA）揭示了丰富的免疫和炎症反应以及生殖激素信号传导的重要网络。最后，对14岁时收集的女性PBMC中的基因表达进行分析，揭示了相关转录物的模块，这些转录物富含免疫和生殖系统功能，并且包括对雌激素和雄激素受体信号传导有反应的基因。雄性DMP位于或接近48个独特的基因中，这些基因富含肾上腺素和去甲肾上腺素生物合成（Enrichr P = 0.021），未发现显著的网络。此外，没有模块被确定使用青春期后的基因表达水平的男性。跨越女性青春期窗口的表观遗传变化可能会对这段时间内发生的激素变化做出反应或改变，并可能导致日后免疫介导和内分泌疾病的性别特异性差异。本文的在线版本（10.1186/s13148-018-0491-2）包含补充材料，可供授权用户使用。
The changes that occur during puberty have been implicated in susceptibility to a wide range of diseases later in life, many of which are characterized by sex-specific differences in prevalence. Both genetic and environmental factors have been associated with the onset or delay of puberty, and recent evidence has suggested a role for epigenetic changes in the initiation of puberty as well. To identify global DNA methylation changes that arise across the window of puberty in girls and boys. Genome-wide DNA methylation levels were measured using the Infinium 450K array. We focused our studies on peripheral blood mononuclear cells (PBMCs) from 30 girls and 25 boys pre- and post-puberty (8 and 14 years, respectively), in whom puberty status was confirmed by Tanner staging. Our study revealed 347 differentially methylated probes (DMPs) in females and 50 DMPs in males between the ages of 8 and 14 years (FDR 5%). The female DMPs were in or near 312 unique genes, which were over-represented for having high affinity estrogen response elements (permutation P < 2.0 × 10−6), suggesting that some of the effects of estrogen signaling in puberty are modified through epigenetic mechanisms. Ingenuity Pathway Analysis (IPA) of the 312 genes near female puberty DMPs revealed significant networks enriched for immune and inflammatory responses as well as reproductive hormone signaling. Finally, analysis of gene expression in the female PBMCs collected at 14 years revealed modules of correlated transcripts that were enriched for immune and reproductive system functions, and include genes that are responsive to estrogen and androgen receptor signaling. The male DMPs were in or near 48 unique genes, which were enriched for adrenaline and noradrenaline biosynthesis (Enrichr P = 0.021), with no significant networks identified. Additionally, no modules were identified using post-puberty gene expression levels in males. Epigenetic changes spanning the window of puberty in females may be responsive to or modify hormonal changes that occur during this time and potentially contribute to sex-specific differences in immune-mediated and endocrine diseases later in life. The online version of this article (10.1186/s13148-018-0491-2) contains supplementary material, which is available to authorized users.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
5.5
作者：
Long MD;Smiraglia DJ;Campbell MJ
通讯作者：
Campbell MJ
DOI：
10.18632/aging.100908
发表时间：
2016-02
期刊：
Aging
影响因子：
--
作者：
Lin Q;Weidner CI;Costa IG;Marioni RE;Ferreira MR;Deary IJ;Wagner W
通讯作者：
Wagner W
影响因子：
3.6
作者：
Gilsanz, Vicente;Hu, Houchun H.;Kajimura, Shingo
通讯作者：
Kajimura, Shingo