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

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 and Yingqun Huang ()
Additional contact information
Jichun Zhou: Gynecology, and Reproductive Sciences, Yale School of Medicine
Lihua Yang: Gynecology, and Reproductive Sciences, Yale School of Medicine
Tianyu Zhong: Gynecology, and Reproductive Sciences, Yale School of Medicine
Martin Mueller: Gynecology, and Reproductive Sciences, Yale School of Medicine
Yi Men: Gynecology, and Reproductive Sciences, Yale School of Medicine
Na Zhang: University of Connecticut Health Center
Juanke Xie: Gynecology, and Reproductive Sciences, Yale School of Medicine
Karolyn Giang: Zymo Research Corporation
Hunter Chung: Zymo Research Corporation
Xueguang Sun: Zymo Research Corporation
Lingeng Lu: Yale School of Public Health, Yale University School of Medicine
Gordon G Carmichael: University of Connecticut Health Center
Hugh S Taylor: Gynecology, and Reproductive Sciences, Yale School of Medicine
Yingqun Huang: Gynecology, and Reproductive Sciences, Yale School of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms10221 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10221

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10221

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().