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The role of DNA methylation: a challenge for the DOHaD paradigm in going beyond the historical debate

Part of: Epigenetics as the Mediator of the Gene/Environment Interactions in DOHAD

Published online by Cambridge University Press:  13 October 2014

S. Ngo  and
A. Sheppard
S. Ngo
Affiliation:
Liggins Institute, University of Auckland, Grafton, Auckland, New Zealand
A. Sheppard*
Affiliation:
Liggins Institute, University of Auckland, Grafton, Auckland, New Zealand
*
*Address for correspondence: A. Sheppard, Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand. (Email [email protected])
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Abstract

A heritage of considerable research into such phenomena as parental imprinting and carcinogenesis is an almost axiomatic association of the DNA methylation epigenetic mark with the silencing of gene expression. However, the increasing technical resolution afforded by burgeoning -omics technologies reveals that a more elaborate interaction may exist between DNA methylation, within sub-regions of gene structure and/or specific dinucleotide sites, and levels of gene activity. Furthermore, seminal observations from the field of DOHaD, which clearly define the alignment of sequential epigenetic modifications and gene activity appear not to support a strictly causal relationship between DNA methylation and gene silencing. The temporal element implicit within DOHaD studies provides a useful framework within which to further explore the role of epigenetic mechanisms and in particular perhaps, to address the question of ‘deterministic intent’ when implicating the epigenetic regulation of gene activity in the manifestation of phenotype.

Keywords

animalhumanlarge animalsmolecular/cellularpregnancy
Type
Commentary
Information
Journal of Developmental Origins of Health and Disease , Volume 6 , Issue 1 , February 2015 , pp. 2 - 4
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2014 

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References

1.Bird, AP. CpG-rich islands and the function of DNA methylation. Nature. 1986; 321, 209–213.Google Scholar
2.Keshet, I, Yisraeli, J, Cedar, H. Effect of regional DNA methylation on gene expression. Proc Natl Acad Sci USA. 1985; 82, 2560–2564.Google Scholar
3.Schubeler, D, Lorincz, MC, Cimbora, DM, et al. Genomic targeting of methylated DNA: influence of methylation on transcription, replication, chromatin structure, and histone acetylation. Mol Cell Biol. 2000; 20, 9103–9112.Google Scholar
4.Bell, O, Tiwari, VK, Thoma, NH, Schubeler, D. Determinants and dynamics of genome accessibility. Nat Rev Genet. 2011; 12, 554–564.CrossRefGoogle ScholarPubMed
5.Jones, PA, Baylin, SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002; 3, 415–428.Google Scholar
6.Jones, PA. The DNA methylation paradox. Trends Genet. 1999; 15, 34–37.Google Scholar
7.Suzuki, MM, Bird, A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet. 2008; 9, 465–476.CrossRefGoogle ScholarPubMed
8.Wagner, JR, Busche, S, Ge, B, et al. The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts. Genome Biol. 2014; 15, R37.Google Scholar
9.Weber, M, Davies, JJ, Wittig, D, et al. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet. 2005; 37, 853–862.Google Scholar
10.Lavebratt, C, Almgren, M, Ekstrom, TJ. Epigenetic regulation in obesity. Int J Obes (Lond). 2012; 36, 757–765.Google Scholar
11.Gluckman, PD, Hanson, MA. Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective. Int J Obes (Lond). 2008; 32, S62–S71.CrossRefGoogle ScholarPubMed
12.Inadera, H. Developmental origins of obesity and type 2 diabetes: molecular aspects and role of chemicals. Environ Health Prev Med. 2013; 18, 185–197.Google Scholar
13.Altobelli, G, Bogdarina, IG, Stupka, E, Clark, AJ, Langley-Evans, S. Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid. PloS One. 2013; 8, e82989.Google Scholar
14.Zhou, Z, Yuan, Q, Mash, DC, Goldman, D. Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol. Proc Nat Acad Sci USA. 2011; 108, 6626–6631.CrossRefGoogle ScholarPubMed
15.Carone, BR, Fauquier, L, Habib, N, et al. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell. 2010; 143, 1084–1096.Google Scholar
16.Sinclair, KD, Allegrucci, C, Singh, R, et al. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Nat Acad Sci USA. 2007; 104, 19351–19356.Google Scholar
17.Lister, R, Pelizzola, M, Dowen, RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009; 462, 315–322.Google Scholar
18.Weber, M, Hellmann, I, Stadler, MB, et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet. 2007; 39, 457–466.Google Scholar
19.Meissner, A, Mikkelsen, TS, Gu, H, et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008; 454, 766–770.CrossRefGoogle ScholarPubMed
20.Park, JH, Stoffers, DA, Nicholls, RD, Simmons, RA. Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest. 2008; 118, 2316–2324.Google Scholar
21.Raynal, NJ, Si, J, Taby, RF, et al. DNA methylation does not stably lock gene expression but instead serves as a molecular mark for gene silencing memory. Cancer Res. 2012; 72, 1170–1181.CrossRefGoogle Scholar
22.Ikegami, K, Ohgane, J, Tanaka, S, Yagi, S, Shiota, K. Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development. Int J Dev Biol. 2009; 53, 203–214.Google Scholar
23.Lee, YM, Chen, HW, Maurya, PK, Su, CM, Tzeng, CR. MicroRNA regulation via DNA methylation during the morula to blastocyst transition in mice. Mol Hum Reprod. 2012; 18, 184–193.Google Scholar
24.Han, L, Witmer, PD, Casey, E, Valle, D, Sukumar, S. DNA methylation regulates microRNA expression. Cancer Biol Ther. 2007; 6, 1284–1288.Google Scholar