Transcriptome and DNA (hydro)methylation in mouse hypothalamic arcuate nucleus in puberty onset.

To better understand the epigenetic mechanism underlying pubertal onset, the hypothalamic genome-wide DNA methylation and hydroxymethylation patterns as well as the transcription profiles in mouse arcuate nucleus at early and late pubertal stages were explored. Female mice have been widely used in multiple studies on pubertal development as they present the similar molecular behaviors in HPG axis and stable cycles of menstrual calendar like human. Hypothalamic ARC underwent a huge epigenetic and genetic reprogramming to adapt to the response and feedback on sexual hormones during the stages of early pubertal (2-5-week of age) and late puberty (5-8-week of age) . We harvested 4- and 8-week hypothalamic ARC and employed RNA-seq, reduced representation bisulfite sequencing (RRBS) and hydroxymethylation profiling (RRHP) on a genome-wide scale. We identified a large number of differential expressed genes (DEGs) and differential 5(h)mC signals across the whole genome. We discovered novel connections between DNA (hydroxyl)methylated modification and gene expression, emphasizing the importance of epigenetic alterations in regulating transcription in puberty onset.

为深入解析青春期启动的表观遗传机制，本研究针对青春期早、晚期小鼠下丘脑弓状核（arcuate nucleus, ARC）的全基因组DNA甲基化、羟甲基化模式及转录谱展开了探究。由于雌性小鼠在下丘脑-垂体-性腺轴（Hypothalamic-Pituitary-Gonadal axis, HPG）中展现出与人类相似的分子调控特征，且拥有类人的稳定月经周期，因此被广泛应用于青春期发育相关的多项研究中。在青春期早期（2~5周龄）与晚期（5~8周龄）阶段，下丘脑弓状核会发生大规模表观遗传与遗传重编程，以适配性激素的应答与反馈调控。本研究采集了4周龄与8周龄小鼠的下丘脑弓状核样本，采用RNA测序（RNA-seq）、简化代表性亚硫酸氢盐测序（RRBS）以及全基因组羟甲基化谱分析（RRHP）进行检测。本研究在全基因组范围内鉴定出大量差异表达基因（DEGs）与差异5(h)mC信号位点。本研究揭示了DNA（羟）甲基化修饰与基因表达之间的全新关联，强调了表观遗传改变在青春期启动的转录调控中发挥的关键作用。