H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase
| Autor: | Hugh S. Taylor, Gordon G. Carmichael, Hunter Chung, Lihua Yang, Tianyu Zhong, Xueguang Sun, Martin Mueller, Lingeng Lu, Karolyn Giang, Juanke Xie, Yi Men, Jichun Zhou, Yingqun Huang, Na Zhang |
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| Rok vydání: | 2015 |
| Předmět: |
Methyltransferase
General Physics and Astronomy 610 Medicine & health Biology Article General Biochemistry Genetics and Molecular Biology Mice chemistry.chemical_compound Insulin-Like Growth Factor II Animals Humans DNA (Cytosine-5-)-Methyltransferases Epigenetics Gene RNA-Directed DNA Methylation Genetics Gene knockdown Genome Multidisciplinary Adenosylhomocysteinase General Chemistry Methylation DNA Methylation S-Adenosylhomocysteine female genital diseases and pregnancy complications chemistry embryonic structures DNA methylation RNA Long Noncoding DNA Protein Binding |
| Zdroj: | Zhou, Jichun; Yang, Lihua; Zhong, Tianyu; Müller, Martin; Men, Yi; Zhang, Na; Xie, Juanke; Giang, Karolyn; Chung, Hunter; Sun, Xueguang; Lu, Lingeng; Carmichael, Gordon G; Taylor, Hugh S; Huang, Yingqun (2015). H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase. Nature communications, 6, p. 10221. Nature Publishing Group 10.1038/ncomms10221 Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. DNA methylation is an important regulatory process and is essential for correct development and physiology. Here the authors show the long non-coding RNA H19 regulates methylation by binding and inhibiting S-adenosylhomocysteine hydrolase. |
| Databáze: | OpenAIRE |
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