ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity

Karen Lillycrop, Robert Murray, Clara Cheong, Ai Ling Teh, Rebecca Clarke-Harris, Sheila Barton, Paula Costello, Emma Garratt, Eloise Cook, Philip Titcombe, Bhuvaneshwari Shunmuganathan, Samantha J Liew, Yong-Cai Chua, Xinyi Lin, Yonghui Wu, Graham C Burdge, Cyrus Cooper, Hazel M Inskip, Neerja Karnani, James C. Hopkins & 14 others Caroline E Childs, Carolina Paras Chavez, Philip C Calder, Fabian Yap, Yung Seng Lee, Yap Seng Chong, Phillip Melton, Lawrence Beilin, Rae-Chi Huang, Peter D Gluckman, Nick Harvey, Mark A Hanson, Joanna D Holbrook, Keith M. Godfrey

Research output: Contribution to journalArticle

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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.

LanguageEnglish
Pages60–72
JournalEBioMedicine
Volume19
DOIs
StatePublished - Mar 2017

Fingerprint

Methylation
Adiposity
DNA Methylation
Genetic Epigenesis
Parturition
Tissue
Association reactions
Long Noncoding RNA
Mutagenesis
Response Elements
Adipose Tissue
Estrogens
Blood
Obesity
Genes
Health
Newborn Infant
Population

Cite this

Lillycrop, K., Murray, R., Cheong, C., Teh, A. L., Clarke-Harris, R., Barton, S., ... Godfrey, K. M. (2017). ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity. EBioMedicine, 19, 60–72. DOI: 10.1016/j.ebiom.2017.03.037
Lillycrop, Karen ; Murray, Robert ; Cheong, Clara ; Teh, Ai Ling ; Clarke-Harris, Rebecca ; Barton, Sheila ; Costello, Paula ; Garratt, Emma ; Cook, Eloise ; Titcombe, Philip ; Shunmuganathan, Bhuvaneshwari ; Liew, Samantha J ; Chua, Yong-Cai ; Lin, Xinyi ; Wu, Yonghui ; Burdge, Graham C ; Cooper, Cyrus ; Inskip, Hazel M ; Karnani, Neerja ; Hopkins, James C. ; Childs, Caroline E ; Chavez, Carolina Paras ; Calder, Philip C ; Yap, Fabian ; Lee, Yung Seng ; Chong, Yap Seng ; Melton, Phillip ; Beilin, Lawrence ; Huang, Rae-Chi ; Gluckman, Peter D ; Harvey, Nick ; Hanson, Mark A ; Holbrook, Joanna D ; Godfrey, Keith M./ ANRIL Promoter DNA Methylation : A Perinatal Marker for Later Adiposity. In: EBioMedicine. 2017 ; Vol. 19. pp. 60–72
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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.",
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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, Melton, P, Beilin, L, Huang, R-C, Gluckman, PD, Harvey, N, Hanson, MA, Holbrook, JD & Godfrey, KM 2017, 'ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity' EBioMedicine, vol 19, pp. 60–72. DOI: 10.1016/j.ebiom.2017.03.037

ANRIL Promoter DNA Methylation : A Perinatal Marker for Later Adiposity. / Lillycrop, Karen; Murray, Robert; Cheong, Clara; Teh, Ai Ling; Clarke-Harris, Rebecca; Barton, Sheila; Costello, Paula; Garratt, Emma; Cook, Eloise; Titcombe, Philip; Shunmuganathan, Bhuvaneshwari; Liew, Samantha J; Chua, Yong-Cai; Lin, Xinyi; Wu, Yonghui; Burdge, Graham C; Cooper, Cyrus; Inskip, Hazel M; Karnani, Neerja; Hopkins, James C.; Childs, Caroline E; Chavez, Carolina Paras; Calder, Philip C; Yap, Fabian; Lee, Yung Seng; Chong, Yap Seng; Melton, Phillip; Beilin, Lawrence; Huang, Rae-Chi; Gluckman, Peter D; Harvey, Nick; Hanson, Mark A; Holbrook, Joanna D; Godfrey, Keith M.

In: EBioMedicine, Vol. 19, 03.2017, p. 60–72.

Research output: Contribution to journalArticle

TY - JOUR

T1 - ANRIL Promoter DNA Methylation

T2 - EBioMedicine

AU - Lillycrop,Karen

AU - Murray,Robert

AU - Cheong,Clara

AU - Teh,Ai Ling

AU - Clarke-Harris,Rebecca

AU - Barton,Sheila

AU - Costello,Paula

AU - Garratt,Emma

AU - Cook,Eloise

AU - Titcombe,Philip

AU - Shunmuganathan,Bhuvaneshwari

AU - Liew,Samantha J

AU - Chua,Yong-Cai

AU - Lin,Xinyi

AU - Wu,Yonghui

AU - Burdge,Graham C

AU - Cooper,Cyrus

AU - Inskip,Hazel M

AU - Karnani,Neerja

AU - Hopkins,James C.

AU - Childs,Caroline E

AU - Chavez,Carolina Paras

AU - Calder,Philip C

AU - Yap,Fabian

AU - Lee,Yung Seng

AU - Chong,Yap Seng

AU - Melton,Phillip

AU - Beilin,Lawrence

AU - Huang,Rae-Chi

AU - Gluckman,Peter D

AU - Harvey,Nick

AU - Hanson,Mark A

AU - Holbrook,Joanna D

AU - Godfrey,Keith M.

PY - 2017/3

Y1 - 2017/3

N2 - 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.

AB - 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.

KW - Adiposity

KW - DNA methylation

KW - Epigenetic

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M3 - Article

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SP - 60

EP - 72

JO - EBioMedicine

JF - EBioMedicine

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Lillycrop K, Murray R, Cheong C, Teh AL, Clarke-Harris R, Barton S et al. ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity. EBioMedicine. 2017 Mar;19:60–72. Available from, DOI: 10.1016/j.ebiom.2017.03.037