H19 LncRNA Alters DNA Methylation Genome Wide by Regulating S-adenosylhomocysteine Hydrolase

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Dec 22

PMID 26687445

Citations 128

Authors

Jichun Zhou

Lihua Yang

Tianyu Zhong

Martin Mueller

Yi Men

Na Zhang

Juanke Xie

Karolyn Giang

Hunter Chung

Xueguang Sun

Lingeng Lu

Gordon G Carmichael

Hugh S Taylor

Yingqun Huang

Affiliations

Soon will be listed here.

Abstract

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.

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