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141401 - ANRIL promoter DNA methylation.pdf (1.11 MB)

ANRIL promoter DNA methylation: a perinatal marker for later adiposity

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journal contribution
posted on 2023-05-20, 18:43 authored by Lillycrop, K, Murray, R, Cheong, C, Teh, AL, Clarke-Harris, R, Barton, S, Costello, P, Garratt, E, Cook, E, Titcombe, P, Shunmuganathan, B, Liew, SJ, Chua, Y-C, Lin, X, Wu, Y, Burdge, GC, Cooper, C, Inskip, HM, Karnani, N, Hopkins, JC, Childs, CE, Chavez, CP, Calder, PC, Yap, F, Lee, YS, Chong, YS, Phillip MeltonPhillip Melton, Beilin, L, Huang, R-C, Gluckman, PD, Harvey, N, Hanson, MA, Holbrook, JD, Godfrey, KM

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.

History

Publication title

EBioMedicine

Volume

19

Pagination

60-72

ISSN

2352-3964

Department/School

Menzies Institute for Medical Research

Publisher

The Lancet Publishing Group

Place of publication

United Kingdom

Rights statement

© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Repository Status

  • Open

Socio-economic Objectives

Neonatal and child health

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