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

Author

Listed:
  • Jichun Zhou

    (Gynecology, and Reproductive Sciences, Yale School of Medicine
    Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine)

  • Lihua Yang

    (Gynecology, and Reproductive Sciences, Yale School of Medicine
    Tianjin Renmin Hospital)

  • Tianyu Zhong

    (Gynecology, and Reproductive Sciences, Yale School of Medicine
    First Affiliated Hospital of Gannan Medical University)

  • Martin Mueller

    (Gynecology, and Reproductive Sciences, Yale School of Medicine
    University Hospital)

  • Yi Men

    (Gynecology, and Reproductive Sciences, Yale School of Medicine
    State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University)

  • Na Zhang

    (University of Connecticut Health Center)

  • Juanke Xie

    (Gynecology, and Reproductive Sciences, Yale School of Medicine
    Reproductive Medical Center, Henan Provincial People’s Hospital)

  • 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)

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.

Suggested Citation

  • 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 Hua, 2015. "H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase," Nature Communications, Nature, vol. 6(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10221
    DOI: 10.1038/ncomms10221
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    Cited by:

    1. Joel I. Perez-Perri & Dunja Ferring-Appel & Ina Huppertz & Thomas Schwarzl & Sudeep Sahadevan & Frank Stein & Mandy Rettel & Bruno Galy & Matthias W. Hentze, 2023. "The RNA-binding protein landscapes differ between mammalian organs and cultured cells," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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