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Abstract

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.

Item Type:	Article
Authors/Creators:	Lillycrop, K and Murray, R and Cheong, C and Teh, AL and Clarke-Harris, R and Barton, S and Costello, P and Garratt, E and Cook, E and Titcombe, P and Shunmuganathan, B and Liew, SJ and Chua, Y-C and Lin, X and Wu, Y and Burdge, GC and Cooper, C and Inskip, HM and Karnani, N and Hopkins, JC and Childs, CE and Chavez, CP and Calder, PC and Yap, F and Lee, YS and Chong, YS and Melton, P and Beilin, L and Huang, R-C and Gluckman, PD and Harvey, N and Hanson, MA and Holbrook, JD and Godfrey, KM
Keywords:	adiposity, DNA methylation, epigenetic
Journal or Publication Title:	EBioMedicine
Publisher:	The Lancet Publishing Group
ISSN:	2352-3964
DOI / ID Number:	10.1016/j.ebiom.2017.03.037
Copyright Information:	© 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/).
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