H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase

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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology

UniBE Contributor:

Müller, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Monika Zehr

Date Deposited:

31 Mar 2016 14:44

Last Modified:

31 Mar 2016 14:44

Publisher DOI:

10.1038/ncomms10221

PubMed ID:

26687445

BORIS DOI:

10.7892/boris.77694

URI:

https://boris.unibe.ch/id/eprint/77694

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