Characterization of Genome-Wide DNA Methylation and Hydroxymethylation in Mouse Arcuate Nucleus of Hypothalamus During Puberty Process.
Characterization of Genome-Wide DNA Methylation and Hydroxymethylation in Mouse Arcuate Nucleus of Hypothalamus During Puberty Process.
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DOI：
10.3389/fgene.2020.626536
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发表时间：
2020
影响因子：
3.7
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Shen Y;Zhou S;Zhao X;Li H;Sun J
背景：由下丘脑促性腺激素释放激素（GnRH）控制的垂体促性腺激素的搏动性分泌是青春期发病所必需的。下丘脑gnrh依赖性调节轴激活的表观遗传机制尚不清楚。本研究旨在探讨DNA（羟基）甲基化特征与青春期发育过程之间的潜在相关性。方法：采用RNA-、RRBS-和rrhp -测序方法，对小鼠青春期早期（4周）和青春期晚期（8周）下丘脑弓状核（ARC）的转录组、差异DNA甲基化和羟甲基化进行全基因组分析。结果：一系列与性发育有关的差异表达基因（DEGs）可分为3个亚群，在启动子区DNA甲基化或羟甲基化或两者均存在显著差异。与DNA甲基化相比，DNA羟甲基化参与了更多的信号通路，包括突触形态、通道活性和胶质细胞发育，可以增强突触间的改变和胶质细胞到神经元的通讯，促进GnRH的释放。转录与这些表观遗传修饰之间的相关性表明，DNA羟甲基化对基因转录的影响独立于青春期DNA甲基化。结论：我们的结果表征了羟甲基化模式，并为青春期过程中基因表达的新表观遗传调控提供了新的见解。
Background: Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic mechanism underlying the activation of GnRH-dependent regulatory axis in hypothalamus remains elusive. This study aims to explore the potential correlation between the signature of DNA (hydroxyl)methylation and pubertal process. Methods: Hypothalamic arcuate nucleus (ARC) of mouse at early (4-weeks) and late pubertal (8-weeks) stages underwent RNA-, RRBS-, and RRHP-seq to investigate the genome-wide profiles of transcriptome, differential DNA methylation and hydroxymethylation. Results: A series of differential expressed genes (DEGs) involved in sexual development could be separated into three subgroups with the significant difference of DNA methylation or hydroxymethylation or both in promoter regions. Compared to DNA methylation, DNA hydroxymethylation partook in more signaling pathways including synapse morphology, channel activity and glial development, which could enhance transsynaptic change and glia-to-neuron communication to faciliate GnRH release. The correlation between transcription and these epigenetic modifications indicated that DNA hydroxymethylation impacted with gene transcription independently of DNA methylation spanning puberty. Conclusion: Our results characterized the hydroxymethylation pattern and provided an insight into the novel epigenetic regulation on gene expression during pubertal process.
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影响因子：
5.7
作者：
Thompson EE;Nicodemus-Johnson J;Kim KW;Gern JE;Jackson DJ;Lemanske RF;Ober C
通讯作者：
Ober C
影响因子：
12.3
作者：
Akalin A;Kormaksson M;Li S;Garrett-Bakelman FE;Figueroa ME;Melnick A;Mason CE
通讯作者：
Mason CE
影响因子：
3.6
作者：
Alves, Bruna R. C.;Cardoso, Rodolfo C.;Amstalden, Marcel
通讯作者：
Amstalden, Marcel
影响因子：
64.5
作者：
Mellen, Marian;Ayata, Pinar;Heintz, Nathaniel
通讯作者：
Heintz, Nathaniel
影响因子：
1.9
作者：
Chulani, Veenod L.;Gordon, Lonna P.
通讯作者：
Gordon, Lonna P.