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    ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity

    Access Status
    Open access via publisher
    Authors
    Lillycrop, K.
    Murray, R.
    Cheong, C.
    Teh, A.
    Clarke-Harris, R.
    Barton, S.
    Costello, P.
    Garratt, E.
    Cook, E.
    Titcombe, P.
    Shunmuganathan, B.
    Liew, S.
    Chua, Y.
    Lin, X.
    Wu, Y.
    Burdge, G.
    Cooper, C.
    Inskip, H.
    Karnani, N.
    Hopkins, J.
    Childs, C.
    Chavez, C.
    Calder, P.
    Yap, F.
    Lee, Y.
    Chong, Y.
    Melton, Phillip
    Beilin, L.
    Huang, R.
    Gluckman, P.
    Harvey, N.
    Hanson, M.
    Holbrook, J.
    Godfrey, K.
    Date
    2016
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Lillycrop, K. and Murray, R. and Cheong, C. and Teh, A. and Clarke-Harris, R. and Barton, S. and Costello, P. et al. 2016. ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity. EBioMedicine.
    Source Title
    EBioMedicine
    DOI
    10.1016/j.ebiom.2017.03.037
    ISSN
    2352-3964
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/58124
    Collection
    • Curtin Research Publications
    Abstract

    © 2017 The Authors. Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth tissues associated with child's adiposity. We identified a novel association between the level of CpG methylation at birth within the promoter of the long non-coding RNA ANRIL (encoded at CDKN2A) and childhood adiposity at age 6-years. An association between ANRIL methylation and adiposity was also observed in three additional populations; in birth tissues from ethnically diverse neonates, in peripheral blood from adolescents, and in adipose tissue from adults. Additionally, CpG methylation was associated with ANRIL expression in vivo, and CpG mutagenesis in vitro inhibited ANRIL promoter activity. Furthermore, CpG methylation enhanced binding to an Estrogen Response Element within the ANRIL promoter. Our findings demonstrate that perinatal methylation at loci relevant to gene function may be a robust marker of later adiposity, providing substantial support for epigenetic processes in mediating long-term consequences of early life environment on human health.

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