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山羊青春期启动过程中DNA甲基化与长链非编码RNA之间的相互作用

The interaction between DNA methylation and long non-coding RNA during the onset of puberty in goats.

作者信息

Yang Chen, Gao Xiaoxiao, Ye Jing, Ding Jianping, Liu Ya, Liu Hongyu, Li Xiumei, Zhang Yunhai, Zhou Jie, Huang Weiping, Fang Fugui, Ling Yinghui

机构信息

Anhui Provincial Laboratory of Animal Genetic Resources Protection and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.

Anhui Provincial Laboratory for Local Livestock and Poultry Genetic Resource Conservation and Bio-Breeding, Hefei, China.

出版信息

Reprod Domest Anim. 2018 Dec;53(6):1287-1297. doi: 10.1111/rda.13246. Epub 2018 Jul 7.

Abstract

Epigenetics plays an important role in controlling female puberty. Both DNA methylation and long non-coding RNAs (lncRNA) regulate the initiation of puberty by affecting the expression of genes related to puberty. While recent studies have indicated that DNA methylation of lncRNA represses the expression of lncRNA, its role in regulating puberty remains unclear. To explore the mechanism between DNA methylation and lncRNAs during puberty onset, we performed whole-genome bisulphite sequencing (WGBS) and RNA-sequencing (RNA-seq). We found that DNA methylation was inversely correlated to gene expression levels during puberty. Methylation levels gradually decreased near the transcription initiation site and were present at high levels in the exon, intron and 3' untranslated regions. In the promoter, lncRNA expression was negatively related to DNA methylation. We reported hypermethylation in the gene body and downstream of the lncRNA compared with upstream regions. In GO and KEGG analyses, we found enriched target genes of lncRNA, XLOC_960044 and XLOC_767346. During puberty, methylation of these genes increased while expression decreased. Our study indicates that DNA methylation of the promoter is negatively correlated with lncRNA during puberty onset, and methylation regulates the initiation of puberty via lncRNA, which provides new insight into the epigenetic mechanism of puberty onset.

摘要

表观遗传学在控制女性青春期方面发挥着重要作用。DNA甲基化和长链非编码RNA(lncRNA)都通过影响与青春期相关基因的表达来调节青春期的启动。虽然最近的研究表明lncRNA的DNA甲基化会抑制lncRNA的表达,但其在调节青春期中的作用仍不清楚。为了探索青春期开始期间DNA甲基化与lncRNAs之间的机制,我们进行了全基因组亚硫酸氢盐测序(WGBS)和RNA测序(RNA-seq)。我们发现青春期期间DNA甲基化与基因表达水平呈负相关。甲基化水平在转录起始位点附近逐渐降低,在外显子、内含子和3'非翻译区中处于高水平。在启动子中,lncRNA表达与DNA甲基化呈负相关。我们报道与上游区域相比,lncRNA的基因体和下游存在高甲基化。在GO和KEGG分析中,我们发现lncRNA XLOC_960044和XLOC_767346的靶基因富集。在青春期,这些基因的甲基化增加而表达降低。我们的研究表明,青春期开始期间启动子的DNA甲基化与lncRNA呈负相关,并且甲基化通过lncRNA调节青春期的启动,这为青春期开始的表观遗传机制提供了新的见解。

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