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Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation
Open accessAbstract
Early nutrition affects adult metabolism in humans and other mammals, potentially via persistent alterations in DNA methylation. With viable yellow agouti (A(vy)) mice, which harbor a transposable element in the agouti gene, we tested the hypothesis that the metastable methylation status of specific transposable element insertion sites renders them epigenetically labile to early methyl donor nutrition. Our results show that dietary methyl supplementation of a/a dams with extra folic acid, vitamin B(12), choline, and betaine alter the phenotype of their A(vy)/a offspring via increased CpG methylation at the A(vy) locus and that the epigenetic metastability which confers this lability is due to the A(vy) transposable element. These findings suggest that dietary supplementation, long presumed to be purely beneficial, may have unintended deleterious influences on the establishment of epigenetic gene regulation in humans.
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“In this case there is a correlation between DNA methylation at the promoter and silencing of the gene [5,6].”
From A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development (2008) · cites this paper as [5]
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Cites
Baron, R. M., & Kenny, D. A. (1986) · Journal of Personality and Social Psychology · doi:10.1037/0022-3514.51.6.1173 · Cited by 91,532
Church, G. M., & Gilbert, W. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.7.1991 · Cited by 8,213
DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124
The fundamental role of epigenetic events in cancer
Jones, P. A., & Baylin, S. B. (2002) · Nature Reviews Genetics · doi:10.1038/nrg816 · Cited by 5,648
Epigenetic Reprogramming in Mammalian Development
Reik, W., Dean, W., & Walter, J. (2001) · Science · doi:10.1126/science.1063443 · Cited by 3,078
Cytosine methylation and the ecology of intragenomic parasites
Yoder, J. A., Walsh, C. P., & Bestor, T. H. (1997) · Trends in Genetics · doi:10.1016/s0168-9525(97)01181-5 · Cited by 1,562
Epigenetic inheritance at the agouti locus in the mouse
Morgan, H. D., Sutherland, H. G. E., Martin, D. I. K., & Whitelaw, E. (1999) · Nature Genetics · doi:10.1038/15490 · Cited by 1,476
Transcription of IAP endogenous retroviruses is constrained by cytosine methylation
Walsh, C. P., Chaillet, J. R., & Bestor, T. H. (1998) · Nature Genetics · doi:10.1038/2413 · Cited by 1,105
Maternal epigenetics and methyl supplements affect agouti gene expression in A vy /a mice
Wolff, G. L., Kodell, R. L., Moore, S. R., & Cooney, C. A. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.11.949 · Cited by 1,057
Programming by Early Nutrition in Man
Lucas, A. (2007) · Novartis Foundation symposium · doi:10.1002/9780470514047.ch4 · Cited by 911
Research works printed but not linked: 1
- Lucas A., 1991, Ciba Found. Symp., 156, 38
Cited by
Sorted by citations
Items 601–700 of 1,002
The Dynamic Nature of DNA Methylation: A Role in Response to Social and Seasonal Variation
Alvarado, S. G., Fernald, R. D., Storey, K. B., & Szyf, M. (2014) · Integrative and Comparative Biology · doi:10.1093/icb/icu034 · Cited by 67
Kotsopoulos, J., Sohn, K., & Kim, Y. (2008) · Journal of Nutrition · doi:10.1093/jn/138.4.703 · Cited by 64
Blaze, J., & Roth, T. L. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.04.004 · Cited by 64
Mechanisms of developmental programming of the metabolic syndrome and related disorders
Luo, Z. (2010) · World Journal of Diabetes · doi:10.4239/wjd.v1.i3.89 · Cited by 63
Vilahur, N., Bustamante, M., Byun, H., Fernández, M. F., Santa‐Marina, L., Basterrechea, M., Ballester, F., Murcia, M., Tardón, A., Fernández‐Somoano, A., et al. (2014) · Environment International · doi:10.1016/j.envint.2014.06.006 · Cited by 63
“327 There is evidence that retrotransposons can serve as alternative promotors in several 328 genes (van de Lagemaat et al. 2003; Waterland and Jirtle 2003).”
BackgroundEpigenetic stochasticity, nuclear structure and cancer: the implications for medicine
Feinberg, A. P. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12224 · Cited by 63
CpG islands: their potential as biomarkers for cancer
Shi, H., Wang, M., & Caldwell, C. W. (2007) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.7.5.519 · Cited by 62
Transcription factor PU.1 is expressed in white adipose and inhibits adipocyte differentiation
Wang, F., & Tong, Q. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00422.2007 · Cited by 63
“Epididymal fat tissues of 3-mo-old Lep mice and 6-mo-old Agouti (A) (45) mice were also used.”
MethodRosenfeld, C. S., Sieli, P. T., Warzak, D. A., Ellersieck, M. R., Pennington, K. A., & Roberts, R. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220230110 · Cited by 63
“The heterogeneity in color of A/a mice stems from differences in the control of expression of the agouti (A) gene, and specifically the A allele (3, 4, 6, 10).”
BackgroundInfluentialPossible roles of zinc nutriture in the fetal origins of disease
Maret, W., & Sandstead, H. H. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.10.005 · Cited by 63
“’’ (Waterland and Jirtle, 2003).”
Choi, Y. S., Kim, S., Lee, H. K., Lee, K.-U., & Pak, Y. K. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.12.065 · Cited by 63
McKay, J. A., Xie, L., Harris, S. E., Wong, Y. K., Ford, D., & Mathers, J. C. (2011) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201100008 · Cited by 62
O’Brien, E., Dolinoy, D. C., & Mancuso, P. (2013) · Journal of Immunotoxicology · doi:10.3109/1547691x.2013.822036 · Cited by 62
Cropley, J. E., Dang, T. H. Y., Martin, D. I. K., & Suter, C. M. (2012) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2011.2646 · Cited by 60
McCullough, L. E., Miller, E. E., Méndez, M. A., Murtha, A. P., Murphy, S. K., & Hoyo, C. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0174-9 · Cited by 68
“Inadequate maternal 1-CC nutrients have been linked to lower DNA methylation at the agouti locus [9] during critical periods of early embryonic development, and in this model epigenetic programs, the offspring to adult obesity, diabetes, and cancer [10].”
BackgroundOECD (2012) · OECD series on testing and assessment · doi:10.1787/9789264221352-en · Cited by 63
Environmental epigenetics and allergic diseases: recent advances
Kuriakose, J., & Miller, R. L. (2010) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2010.03599.x · Cited by 61
“[4–6] Alternatively, epigenetic modifications may occur postnatally leading to sustained effects on gene transcription.”
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Lillycrop, K. A., Hoile, S. P., Grenfell, L. R., & Burdge, G. C. (2014) · Proceedings of The Nutrition Society · doi:10.1017/s0029665114000081 · Cited by 64
“DNA methylation is essential for normal development; it is responsible for the asymmetrical silencing of imprinted genes((7)), X-chromosome inactivation((8,9)) and for the tissue-specific gene expression((3)).”
BackgroundGenomic signatures of diet-related shifts during human origins
Babbitt, C. C., Warner, L., Fedrigo, O. D., Wall, C. E., & Wray, G. A. (2010) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2010.2433 · Cited by 61
Epigenetic alterations in sperm associated with male infertility
Kitamura, A., Miyauchi, N., Hamada, H., Hiura, H., Chiba, H., Okae, H., Satô, A., John, R. M., & Arima, T. (2015) · Congenital Anomalies · doi:10.1111/cga.12113 · Cited by 66
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Issa, J. J. (2008) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0029 · Cited by 61
“It is speculated that dietary interventions may alter DNA methylation or histone modifications, but such dietary effects may be greatest during embryogenesis and early development (33).”
BackgroundInferring Past Environments from Ancient Epigenomes
Gokhman, D., Malul, A., & Carmel, L. (2017) · Molecular Biology and Evolution · doi:10.1093/molbev/msx211 · Cited by 59
Szeto, I. M. Y., Aziz, A. A., Das, P., Taha, A. Y., Okubo, N., Reza‐López, S. A., Giacca, A., & Anderson, G. H. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90354.2008 · Cited by 60
“Increased cytosine methylation of the A gene has been found after pregnant mice were fed high dietary levels of methyl donors (betaine and choline) or methyl metabolism cofactors (folate and vitamin B12) (56), which led to a change in the coat color of the offspring (57, 59).”
BackgroundThe Genetic and Environmental Causes of Pulmonary Fibrosis
Macneal, K., & Schwartz, D. A. (2012) · Proceedings of the American Thoracic Society · doi:10.1513/pats.201112-055aw · Cited by 59
Nutritional regulation of fetal growth and implications for productive life in ruminants
Symonds, M. E., Sebert, S. P., & Budge, H. (2010) · animal · doi:10.1017/s1751731110000479 · Cited by 63
“To date, all of the experimental evidence relating to this process has been largely confined to studies using rodents with extreme dietary modifications such as consumption of a hypermethylating diet through pregnancy and lactation (Waterland and Jirtle, 2003) that contains a , 9-fold increase in choline and folic aci…”
BackgroundThe role of nutrition in cancer development and prevention
Michels, K. B. (2004) · International Journal of Cancer · doi:10.1002/ijc.20662 · Cited by 60
Yang, B., Bhusari, S. S., Kueck, J., Weeratunga, P., Wagner, J. L., LEVERSON, G. E., Huang, W., & Jarrard, D. F. (2013) · Neoplasia · doi:10.1593/neo.13280 · Cited by 59
“Further research will be needed to address this hypothesis and how a widespread methylation field defect might arise, whether due to diet or environmental exposures [32,33].”
BackgroundUnderstanding confounding and mediation
Babyak, M. A. (2009) · Evidence-Based Mental Health · doi:10.1136/ebmh.12.3.68 · Cited by 59
“The context was an experiment that examined the effect of diet on coat colour in a special breed of mice.(5) This was highly sophisticated work involving genotyping and a number of other technical details of which I have only a faint grasp, but the gist of the experiment was this.”
BackgroundAlvarado, S. G., Mak, T., Liu, S. W., Storey, K. B., & Szyf, M. (2015) · Journal of Experimental Biology · doi:10.1242/jeb.116046 · Cited by 60
“, 2004), different diets (Bollati et al., 2007; Waterland and Jirtle, 2003) or toxins could alter DNA methylation, it is unclear whether these constitute stochastic responses to signals modulating DNA methylation enzymes or whether there is an organized programmed genomic response to distinct and predictable environme…”
BackgroundGoodman, J. I., Augustine, K. A., Cunnningham, M. L., Dixon, D., Dragan, Y. P., Falls, J. G., Rasoulpour, R. J., Sills, R. C., Storer, R. D., Wolf, D. C., et al. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq133 · Cited by 59
Distinctions between transgenerational and non-transgenerational epimutations
McCarrey, J. R. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.07.016 · Cited by 58
“…induced by environmental factors including poor nutrition (Barker, 2004; Lillycrop et al., 2005), exposure to ethanol (Elliott et al., 2006), methyl donors (Lambrot et al., 2013; Waterland and Jirtle, 2003), glucocorticoids (Drake et al., 2005) or endocrine disruptors (Nilsson and Skinner, 2014).”
Mother–child transmission of epigenetic information by tunable polymorphic imprinting
Carpenter, B. L., Zhou, W., Madaj, Z., DeWitt, A. K., Ross, J. P., Grønbæk, K., Liang, G., Clark, S. J., Molloy, P. L., & Jones, P. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1815005115 · Cited by 56
Long term effects of pre- and early postnatal nutrition and environment on the gut1
Lallès, J. P. (2012) · Journal of Animal Science · doi:10.2527/jas.53904 · Cited by 61
Fetal Programming of Cardiac Function and Disease
Meyer, K., & Zhang, L. (2007) · Reproductive Sciences · doi:10.1177/1933719107302324 · Cited by 58
Wakeling, L. A., Ions, L. J., & Ford, D. (2009) · AGE · doi:10.1007/s11357-009-9104-5 · Cited by 63
An epigenetic analysis of SOD1 and VEGF in ALS
Oates, N., & Pamphlett, R. (2007) · Amyotrophic Lateral Sclerosis · doi:10.1080/17482960601149160 · Cited by 59
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BackgroundAnckaert, E., Romero, S., Adriaenssens, T., & Smitz, J. E. J. (2010) · Biology of Reproduction · doi:10.1095/biolreprod.109.082164 · Cited by 60
“In mice, supraphysiological maternal dietary methyl group supplementation (before and during pregnancy) induced a DNA hypermethylation at the viable yellow agouti and at the axin fused metastable epialleles in the offspring [20, 21].”
BackgroundMicroarray analysis reveals global modulation of endogenous retroelement transcription by microbes
Young, G. R., Mavrommatis, B., & Kassiotis, G. (2014) · Retrovirology · doi:10.1186/1742-4690-11-59 · Cited by 61
“Thus, while the potential impact of REs in infection and disease is a large area of current study, research is complicated by the scarcity of data describing their natural spatial and temporal patterns of transcription, and responsiveness to ubiquitous stimuli, including elements of diet [19].”
BackgroundEpigenetics, nutrition and mental health. Is there a relationship?
Stevens, A. J., Rucklidge, J. J., & Kennedy, M. A. (2017) · Nutritional Neuroscience · doi:10.1080/1028415x.2017.1331524 · Cited by 61
Juriloff, D. M., Harris, M. J., Dewell, S. L., Brown, C. J., Mager, D. L., Gagnier, L., & Mah, D. G. (2005) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20106 · Cited by 58
Early‐life influences on obesity: from preconception to adolescence
Wahlqvist, M. L., Krawetz, S. A., Rizzo, N., Domínguez-Bello, M. G., Szymanski, L. M., Barkin, S. L., Yatkine, A., Waterland, R. A., Mennella, J. A., Desai, M., et al. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12778 · Cited by 59
Session 2: Personalised nutrition Epigenomics: a basis for understanding individual differences?
Mathers, J. C. (2008) · Proceedings of The Nutrition Society · doi:10.1017/s0029665108008744 · Cited by 61
“Higher intakes of methyl donors (folic acid, vitamin B12, choline and betaine) by the dams increase the proportion of mottled and pseudo-agouti offspring, which is accompanied by greater methylation of the cryptic promoter in the proximal end of the A intracisternal A-particle((14)).”
InfluentialBuscariollo, D. L., Fang, X., Greenwood, V., Xue, H., Rivkees, S. A., & Wendler, C. C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087547 · Cited by 57
“Changes in DNA methylation patterns occurring normally during early embryogenesis can be influenced by nutritional and environmental factors resulting in long lasting effects in adulthood [34–36].”
BackgroundLevin, B. E. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.02.005 · Cited by 59
Folate and Cancer Prevention—Where to Next? Counterpoint
Ulrich, C. M. (2008) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-07-2952 · Cited by 56
“However, data are sparse and conflicting on whether folate status affects promoter methylation of specific genes or the CpG island methylator phenotype, which characterizes tumors with widespread hypermethylation of gene promoters (12-18).”
BackgroundEpigenetic modulation and cancer: effect of metabolic syndrome?
Ross, S. A., & Milner, J. A. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.3.872s · Cited by 59
“Another research team has also examined the effect of methyl donor supplementation (folic acid, vitamin B-12, choline, and betaine) to the maternal diet without zinc in the agouti model and found similar effects on the phenotypic expression of the offspring (40).”
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Ueda, J., Maehara, K., Mashiko, D., Ichinose, T. M., Yao, T., Hori, M., Sato, Y., Kimurâ, H., Ohkawa, Y., & Yamagata, K. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.05.008 · Cited by 57
Maternal-foetal epigenetic interactions in the beginning of cardiovascular damage
Claudio Napoli, A., Infante, T., & Casamassimi, A. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr201 · Cited by 57
Epigenetic Programming by Maternal Nutrition: Shaping Future Generations
Li, C. C. Y., Maloney, C., Cropley, J. E., & Suter, C. M. (2010) · Epigenomics · doi:10.2217/epi.10.33 · Cited by 57
Genome-wide DNA Methylation in Human Heart Failure
Movassagh, M., Vujić, A., & Foo, R. (2011) · Epigenomics · doi:10.2217/epi.10.70 · Cited by 56
Holmes, L., Lim, A. C., Comeaux, C. R., DABNEY, K. W., & Okundaye, O. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16234829 · Cited by 56
Lecorguillé, M., Teo, S. M., & Phillips, C. M. (2021) · Nutrients · doi:10.3390/nu13093130 · Cited by 58
“One study showed that methyl-donor supplementation (folic acid, vitamin B12, choline and betaine) was associated with hypermethylation of the agouti gene [160].”
BackgroundColwell, M., Townsel, C., Petroff, R., Goodrich, J. M., & Dolinoy, D. C. (2023) · Exposome · doi:10.1093/exposome/osad001 · Cited by 64
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Chen, J., & Xu, X. (2010) · Advances in genetics · doi:10.1016/b978-0-12-380864-6.00008-0 · Cited by 57
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Labbé, D. P., Zadra, G., Ebot, E. M., Mucci, L. A., Kantoff, P. W., Loda, M. F., & Brown, M. A. (2014) · Oncogene · doi:10.1038/onc.2014.422 · Cited by 56
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Green, R. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26947e · Cited by 55
“Another possible consequence of increased folic acid intake is an alteration in epigenetic programming in utero (15, 16).”
BackgroundTransgenerational Epigenetic Inheritance: Adaptation Through the Germline Epigenome?
Prokopuk, L., Western, P. S., & Stringer, J. M. (2015) · Epigenomics · doi:10.2217/epi.15.36 · Cited by 57
Faulk, C. D., Kim, J. H., Anderson, O. S., Nahar, M. S., Jones, T. R., Sartor, M. A., & Dolinoy, D. C. (2016) · Epigenetics · doi:10.1080/15592294.2016.1183856 · Cited by 57
“Mice were obtained from a colony carrying the agouti viable yellow (A) epigenetic allele and the non-agouti (a) allele in a forced heterozygous state.(41) This colony consists of a/a and A/a congenic mice with 93% sequence identity to the C57Bl/ 6J strain.”
MethodImpact of diets and nutrients/drugs on early epigenetic programming
Junien, C. (2005) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-006-0299-7 · Cited by 56
“Waterland also showed that coat colour phenotype and AVY methylation pattern persisted into adulthood (Waterland and Jirtle 2003).”
BackgroundEpigenetic susceptibility factors for prostate cancer with aging
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“A classic study involved the Agouti mouse in which folate supplementation of the pregnant dam alters DNA methylation of a retroposon resulting in altered coat color in the offspring [46].”
Szeto, I. M. Y., Das, P., Aziz, A. A., & Anderson, G. H. (2009) · International Journal of Obesity · doi:10.1038/ijo.2008.281 · Cited by 54
Epigenetic mechanisms underlying cardiac degeneration and regeneration
Chaturvedi, P., & Tyagi, S. C. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.02.008 · Cited by 59
“The maternal diet during pregnancy, can dramatically affect the DNA methylation pattern of specific genes which lead to permanent phenotypic changes such as body weight, blood pressure and coat color [160, 161].”
BackgroundThe aetiology of obesity beyond eating more and exercising less
Dhurandhar, E. J., & Keith, S. W. (2014) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2014.07.001 · Cited by 61
“In agouti mice, methyl supplementation of the maternal diet influences methylation of the Avy allele and offspring obesity [23].”
BackgroundChen, C., Lee, K., Pai, M.-Y., Chu, P., Hsu, C., Chiu, C.-C., Chen, L., Chang, J., Hsiao, S., & Leu, Y. (2015) · Cancer Cell International · doi:10.1186/s12935-015-0248-3 · Cited by 57
“Also, various concentrations of diets given to pregnant mice can lead to production of the methylation source S-adenosylmethionine (SAM), altering methylation level at the promoter regions of fur color reporter genes and causing variegated fur color in the offspring [7–9].”
Zhang, B., Zhang, Y., Wang, X., Zhang, H., & Lin, Q. (2017) · Ecology and Evolution · doi:10.1002/ece3.3067 · Cited by 56
“Transposable elements can influence neighboring genes by altering splicing and polyadenylation patterns, or by functioning as enhancers or promoters (Girard & Freeling, 1999; Slotkin & Martienssen, 2007; Waterland & Jirtle, 2003).”
BackgroundNUTRITION AND CANCER PREVENTION: A Multidisciplinary Perspective on Human Trials
Forman, M. R., Hursting, S. D., Umar, A., & Barrett, J. C. (2004) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.24.012003.132315 · Cited by 54
Chromatin modifications in metabolic disease: Potential mediators of long‐term disease risk
Costello, K. R., & Schones, D. E. (2018) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1416 · Cited by 52
“However, this effect is only transmitted over two generations, indicating that it is intergenerational as opposed to transgenerational (see further discussion below) (Waterland & Jirtle, 2003).”
BackgroundEarly life, the epigenome and human health
Szyf, M. (2009) · Acta Paediatrica · doi:10.1111/j.1651-2227.2009.01382.x · Cited by 55
“This ‘early life environment’ hypothesis might provide a plausible explanation for the rapid emergence of certain late onset diseases such as obesity, type II diabetes and asthma in the past century (6).”
BackgroundMaternal DNA hypomethylation and congenital heart defects
Chowdhury, S., Cleves, M. A., MacLeod, S. L., James, S. J., Zhao, W., & Hobbs, C. A. (2011) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20761 · Cited by 55
Folate status and colorectal cancer risk: A 2016 update
Mason, J. B., & Tang, S. Y. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.11.010 · Cited by 54
“…coat color from yellow 253 to brown in conjunction with de-novo methylation of specific sequences in the 254 agouti gene (Cooney et al, 2002; Waterland and Jirtle, 2003) Also, maternal 255 plasma folate concentrations in humans were shown to concur with nearly 50 256 CpG sites in cord…”
BackgroundHypoxia-Mediated Epigenetic Regulation of Stemness in Brain Tumor Cells
Prasad, P., Mittal, S. A., Chongtham, J., Mohanty, S., & Srivastava, T. (2017) · Stem Cells · doi:10.1002/stem.2621 · Cited by 54
Urbanization is associated with modifications in DNA methylation in a small passerine bird
Watson, H., Powell, D., Salmón, P., Jacobs, A., & Isaksson, C. (2020) · Evolutionary Applications · doi:10.1111/eva.13160 · Cited by 53
“Despite this suggested reversible plasticity, there is evidence that, if epigenetic modifications occur in early life, phenotypic traits can be permanently affected (Waterland & Jirtle, 2003; Weaver et al., 2004) with consequences for fitness (Rubenstein et al., 2016).”
BackgroundMitochondria‐Based Model for Fetal Origin of Adult Disease and Insulin Resistance
Lee, H. K., Park, K. S., Cho, Y. M., Lee, Y. Y., & Pak, Y. K. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1338.001 · Cited by 53
Prentice, S. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01641 · Cited by 52
Stenvinkel, P. (2014) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfu338 · Cited by 54
“When pregnant mice were fed methylrich food (choline, folic acid, betaine and vitamin B12), this increased the methylation of the locus and silenced the gene expression, which resulted in lean brown Agouti mice with low disease risk [82].”
BackgroundEpigenetic mechanisms in health and disease
van der Maarel, S. M. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.098392 · Cited by 51
Epigenetic maturation in colonic mucosa continues beyond infancy in mice
Kellermayer, R., Balasa, A., Zhang, W., Lee, S. F., Mirza, S., Chakravarty, A., Szigeti, R. G., Laritsky, E., Tatevian, N., Smith, C. W., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq095 · Cited by 52
“Accordingly, mouse models have shown that intrauterine (10,11) and even postnatal (12) dietary influences affect the establishment of epigenetic mechanisms at specific genomic loci, leading to permanent phenotypic changes.”
BackgroundMethodInfluentialHuang, M. C., Douillet, C., Dover, E. N., & Stýblo, M. (2018) · Archives of Toxicology · doi:10.1007/s00204-018-2206-z · Cited by 52
“Maternal folate and/or B12 supplementation has previously been reported to affect DNA methylation in offspring (Cooney et al. 2002; Waterland and Jirtle 2003; Yadav et al. 2018) and to alter body weight, glucose tolerance, insulin resistance, and expression of genes regulating food intake in rat offspring (Cho et al.”
Moore, D. S. (2016) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1333 · Cited by 55
“Specifically, providing pregnant mice of this strain with a diet containing supplemental methyl groups causes pups developing in utero to be more likely to develop brownish coats and healthy constitutions; the supplemented diet contributes to DNA methylation in the not-yet-born offspring, which silences DNA that contr…”
BackgroundShimizu, Y., Sakata‐Haga, H., Saikawa, Y., & Hatta, T. (2023) · Cells · doi:10.3390/cells12050741 · Cited by 52
Sandovici, I., Hammerle, C. M., Ozanne, S. E., & Constância, M. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1297-1 · Cited by 52
“Current studies also suggest that environmentally induced epigenetic alterations affect not only promoters of protein-coding genes [reviewed in 10, 11] but also transposable elements such as the IAP element at the A locus [86], and regulatory elements such as the enhancer region located downstream the Avp (arginine va…”
Epidemiology of asthma: risk factors for development
Subbarao, P., Becker, A. B., Brook, J. R., Daley, D., Mandhane, P. J., Miller, G. E., Turvey, S. E., & Sears, M. R. (2008) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.5.1.77 · Cited by 55
Meems, L. M. G., Mahmud, H., Buikema, H., Tost, J., Michel, S., Takens, J., Verkaik‐Schakel, R. N., Vreeswijk‐Baudoin, I., Leach, I. M., van der Harst, P., et al. (2016) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00141.2016 · Cited by 51
Folate deficiency as predisposing factor for childhood leukaemia: a review of the literature
Cantarella, C. D., Ragusa, D., Giammanco, M., & Tosi, S. (2017) · Genes & Nutrition · doi:10.1186/s12263-017-0560-8 · Cited by 52
Superoxide dismutase 1 knockdown induces oxidative stress and DNA methylation loss in the prostate
Bhusari, S. S., Dobosy, J. R., Fu, V., Almassi, N., Oberley, T., & Jarrard, D. F. (2010) · Epigenetics · doi:10.4161/epi.5.5.11853 · Cited by 50
Consequences of dietary methyl donor supplements: Is more always better?
Shorter, K. R., Felder, M. R., & Vrana, P. B. (2015) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2015.03.007 · Cited by 51
Epigenetics: Sins of the fathers, and their fathers
Whitelaw, E. (2006) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201567 · Cited by 52
Caizergues, A. E., Luyer, J. L., Grégoire, A., Szulkin, M., Señar, J. C., Charmantier, A., & Perrier, C. (2021) · Evolutionary Applications · doi:10.1111/eva.13334 · Cited by 50
“Such methylation- linked phenotypic variation can occur during an individual's lifetime, especially early on during the organism's development (Waterland & Jirtle, 2003; Weaver et al., 2004).”
BackgroundAdversity before conception will affect adult progeny in rats.
Shachar-Dadon, A., Schulkin, J. A., & Leshem, M. (2009) · Developmental Psychology · doi:10.1037/a0014030 · Cited by 52
Dnmt3a in Sim1 Neurons Is Necessary for Normal Energy Homeostasis
Kohno, D., Lee, S., Harper, M. J., Kim, K. W., Sone, H., Sasaki, T., Kitamura, T., Fan, G., & Elmquist, J. K. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1316-14.2014 · Cited by 52
“Importantly, de novo DNA methylation actively occurs under the influence of extrinsic factors during development (Waterland and Jirtle, 2003; Jirtle and Skinner, 2007; Feil and Fraga, 2011), suggesting that methylation is critical for proper growth.”
BackgroundHuang, S. K., Scruggs, A. M., Donaghy, J., McEachin, R. C., Fisher, A. S., Richardson, B. C., & Peters-Golden, M. L. (2012) · The FASEB Journal · doi:10.1096/fj.11-203323 · Cited by 49
“Diet and levels of micronutrients, such as folate, have been shown to exert a profound effect on the methylation patterns found in mothers and their offspring (2, 32).”
BackgroundEmerging Issues in Public Health Genomics
Roberts, J. S., Dolinoy, D. C., & Tarini, B. A. (2014) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090413-025514 · Cited by 53
Epigenetics changes associated to environmental triggers in autoimmunity
Cañas, C. A., Cañas, F., Bonilla‐Abadía, F., Ospina, F. E., & Tobón, G. J. (2015) · Autoimmunity · doi:10.3109/08916934.2015.1086996 · Cited by 49
Metastable epialleles and their contribution to epigenetic inheritance in mammals
Bertozzi, T. M., & Ferguson‐Smith, A. C. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.08.002 · Cited by 50
Bacon, E. R., & Brinton, R. D. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.040 · Cited by 52
“Interestingly, these offspring were also less prone to obesity and other diseases (Waterland and Jirtle, 2003).”
BackgroundDesiere, F. (2004) · Biotechnology annual review · doi:10.1016/s1387-2656(04)10003-3 · Cited by 50
Epigenetics of Complex Diseases: From General Theory to Laboratory Experiments
Schumacher, A., & Petronis, A. (2006) · Springer eBooks · doi:10.1007/3-540-31181-5_6 · Cited by 50
“The epigenetic status of genes and genomes is far more dynamic in comparison to theDNAsequence and is subject to changes under the influence of developmental programs and the internal and external environment of the organism (Cooney et al. 2002; Sutherland and Costa 2003; Waterland and Jirtle 2003; Weaver et al. 2004).”
BackgroundThe Potential of Epigenetics Research to Transform Conceptions of Phenotype Development
Moore, D. S. (2017) · Human Development · doi:10.1159/000477992 · Cited by 49
“…wherein a particular experience causes changes in genetic activity via alterations of so-called epigenetic marks, chemical groups that become attached to DNA itself or to proteins closely associated with DNA [Provençal et al., 2012; Tung et al., 2012; Waterland & Jirtle, 2003; Weaver et al., 2004].”
BackgroundSugar ecologies: their metabolic and racial effects
Hatch, A. R., Sternlieb, S. R., & Gordon, J. T. (2019) · Food Culture & Society · doi:10.1080/15528014.2019.1638123 · Cited by 50
“Studies have shown that early exposure to specific nutrientdeficient or -enriched diets affect methylation patterns of metabolic genes later in life (Waterland and Jirtle 2003), namely including the insulin-like-growth factor 2 gene (Igf2) which is crucial for insulin production and regulation…”
Background
Metadata
- Authors
- Waterland, R. A., & Jirtle, R. L.
- Affiliations
- Duke Medical Center (US)
- Corresponding author
- Jirtle, Randy L.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2003-08-01
- Volume
- 23
- Issue
- 15
- Pages
- 5293-5300
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC165709
- OpenAlex
- W2100489386
- Cited by
- 2,019
- References
- 35
- Citations by year
- 2026: 30 · 2025: 47 · 2024: 54 · 2023: 37 · 2022: 82 · 2021: 68 · 2020: 38 · 2019: 75 · 2018: 76 · 2017: 88 · 2016: 93 · 2015: 110 · 2014: 143 · 2013: 130 · 2012: 144
- FWCI
- 22.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA025951, CA25951)
- National Institute of Environmental Health Sciences (ES08823, R01ES008823)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Keywords
- transposable elements, DNA methylation, epigenetic inheritance, early life nutrition, methyl donor supplementation, folic acid, vitamin B12, choline, betaine, agouti gene, CpG methylation, maternal diet, offspring phenotype
- MeSH terms
- Alleles, Animals, Betaine, Choline, DNA Transposable Elements, Exons, Folic Acid, Gene Expression Regulation, Mice, Inbred C3H, Mice, Inbred C57BL, Models, Genetic, Molecular Sequence Data, Nutritional Physiological Phenomena, Phenotype, Sulfites, Vitamin B 12, Polymerase Chain Reaction, Sequence Analysis, DNA, CpG Islands, DNA Methylation, Dietary Supplements, Mice
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