Shen Yihang, Zhao Hongchao, Zhang Lei, Hu Yanping, Cai Li, Li Jun, Zhou Shasha
Department of Central Laboratory, Suzhou Ninth People's Hospital, Suzhou, Jiangsu 215200, China.
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, China.
Mol Ther Nucleic Acids. 2021 Jul 21;26:242-252. doi: 10.1016/j.omtn.2021.07.006. eCollection 2021 Dec 3.
Puberty is the gateway to adult reproductive competence, encompassing a suite of complex, integrative, and coordinated changes in neuroendocrine functions. However, the regulatory mechanisms of transcriptional reprogramming in the arcuate nucleus (ARC) during onset of puberty are still not fully understood. To understand the role of epigenetics in regulating gene expression, mouse hypothalamic ARCs were isolated at 4 and 8 weeks, and the transcriptome, DNA hydroxymethylation, DNA methylation, and chromatin accessibility were assessed via RNA sequencing (RNA-seq), reduced representation bisulfite sequencing (RRBS-seq), reduced representation hydroxymethylation profiling (RRHP)-seq, and assay for transposase-accessible chromatin (ATAC-seq), respectively. The overall DNA hydroxymethylation and DNA methylation changes in retroelements (REs) were associated with gene expression modeling for puberty in the ARC. We focused on analyzing DNA hydroxymethylation and DNA methylation at two short interspersed nuclear elements (SINEs) located on the promoter of the 5-hydroxytryptamine receptor 6 () gene and the enhancer of the KISS-1 metastasis suppressor () gene and investigated their regulatory roles in gene expression. Our data uncovered a novel epigenetic mechanism by which SINEs regulate gene expression during puberty.
青春期是通向成年生殖能力的大门，包含一系列神经内分泌功能的复杂、综合和协调变化。然而，青春期开始时弓状核（ARC）中转录重编程的调控机制仍未完全了解。为了了解表观遗传学在调节基因表达中的作用，在4周和8周时分离小鼠下丘脑ARC，并分别通过RNA测序（RNA-seq）、简化代表性亚硫酸氢盐测序（RRBS-seq）、简化代表性羟甲基化分析（RRHP）-seq和转座酶可及染色质分析（ATAC-seq）评估转录组、DNA羟甲基化、DNA甲基化和染色质可及性。逆转录元件（REs）中整体DNA羟甲基化和DNA甲基化变化与ARC中青春期的基因表达模型相关。我们着重分析位于5-羟色胺受体6（）基因启动子和KISS-1转移抑制因子（）基因增强子上的两个短散在核元件（SINEs）处的DNA羟甲基化和DNA甲基化，并研究它们在基因表达中的调控作用。我们的数据揭示了一种新的表观遗传机制，即SINEs在青春期调节基因表达。
