H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase.,Nature Communications

当前位置： X-MOL 学术 › Nat. Commun. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase.
Nature Communications ( IF 14.7 ) Pub Date : 2015-Dec-21 , DOI: 10.1038/ncomms10221
Jichun Zhou _{1,

2} , Lihua Yang _{1,

3} , Tianyu Zhong _{1,

4} , Martin Mueller _{1,

5} , Yi Men _{1,

6} , Na Zhang ₇ , Juanke Xie _{1,

8} , Karolyn Giang ₉ , Hunter Chung ₉ , Xueguang Sun ₉ , Lingeng Lu ₁₀ , Gordon G Carmichael ₇ , Hugh S Taylor ₁ , Yingqun Huang ₁

Affiliation

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut 06510, USA.
Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
Department of Obstetrics and Gynecology, Tianjin Renmin Hospital, Tianjin 300000, China.
Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China.
Department of Obstetrics and Gynecology, University Hospital, Bern 3012, Switzerland.
Department of Head and Neck Surgery, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Reproductive Medical Center, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China.
Zymo Research Corporation, Irvine, California 92614, USA.
Department of Chronic Diseases Epidemiology, Yale School of Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

DNA methylation is essential for mammalian development and physiology. Here we report that the developmentally regulated H19 lncRNA binds to and inhibits S-adenosylhomocysteine hydrolase (SAHH), the only mammalian enzyme capable of hydrolysing S-adenosylhomocysteine (SAH). SAH is a potent feedback inhibitor of S-adenosylmethionine (SAM)-dependent methyltransferases that methylate diverse cellular components, including DNA, RNA, proteins, lipids and neurotransmitters. We show that H19 knockdown activates SAHH, leading to increased DNMT3B-mediated methylation of an lncRNA-encoding gene Nctc1 within the Igf2-H19-Nctc1 locus. Genome-wide methylation profiling reveals methylation changes at numerous gene loci consistent with SAHH modulation by H19. Our results uncover an unanticipated regulatory circuit involving broad epigenetic alterations by a single abundantly expressed lncRNA that may underlie gene methylation dynamics of development and diseases and suggest that this mode of regulation may extend to other cellular components.

中文翻译：

H19 lncRNA 通过调节 S-腺苷高半胱氨酸水解酶改变基因组范围内的 DNA 甲基化。

DNA 甲基化对于哺乳动物的发育和生理至关重要。在这里，我们报告发育调控的 H19 lncRNA 结合并抑制 S-腺苷高半胱氨酸水解酶 (SAHH)，这是唯一能够水解 S-腺苷高半胱氨酸 (SAH) 的哺乳动物酶。 SAH 是 S-腺苷甲硫氨酸 (SAM) 依赖性甲基转移酶的有效反馈抑制剂，该酶可甲基化多种细胞成分，包括 DNA、RNA、蛋白质、脂质和神经递质。我们发现，H19 敲低会激活 SAHH，导致 Igf2-H19-Nctc1 基因座内 DNMT3B 介导的 lncRNA 编码基因 Nctc1 甲基化增加。全基因组甲基化分析揭示了许多基因位点的甲基化变化，与 H19 的 SAHH 调节一致。我们的结果揭示了一个意想不到的调节回路，涉及单个丰富表达的lncRNA的广泛表观遗传改变，这可能是发育和疾病的基因甲基化动态的基础，并表明这种调节模式可能扩展到其他细胞成分。

更新日期：2015-12-24

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南