{"id":307898,"date":"2025-08-01T00:31:12","date_gmt":"2025-08-01T00:31:12","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/307898\/"},"modified":"2025-08-01T00:31:12","modified_gmt":"2025-08-01T00:31:12","slug":"scientists-answer-a-20-year-old-question-in-epigenetics","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/307898\/","title":{"rendered":"Scientists answer a 20-year-old question in epigenetics"},"content":{"rendered":"

\t\"\"Epigenetics is a system of molecular tags (orange squiggles) \u2013 such as methyl groups \u2013 that are added to DNA during development to determine gene expression in different cell types.<\/strong> NHGRI<\/p>\n

Among genetically identical \u2018agouti viable yellow\u2019 (Avy) mice, some are brown and lean while others are yellow and obese. These differences are due to epigenetics, a system of molecular tags \u2013 such as methyl groups \u2013 that are added to DNA during development to determine gene expression in different cell types. A 2003 study<\/a> showed that simply supplementing the diet of female mice with \u2018methyl donor\u2019 nutrients before and during pregnancy caused more of their Avy offspring to turn out lean and brown.<\/p>\n

The Avy gene is known as a \u2018metastable epiallele,\u2019 because its level of DNA methylation is established randomly during early embryonic development. The 2003 study raised the idea that metastable epialleles might be common in mice, offering a potential explanation for many examples of unexplained variation among inbred mice (such as differences in weight gain on a high-fat diet). Despite a few small studies, however, the number of metastable epialleles in mice remained unknown for more than 20 years.<\/p>\n

\"\"<\/a>Dr. Robert A. Waterland<\/strong><\/p>\n

A new study by a team of researchers led by corresponding author Dr. Robert A. Waterland<\/a>, professor of pediatrics-nutrition and member of the USDA\/ARS Children\u2019s Nutrition Research Center and the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine now shows that metastable epialleles in mice are extremely rare. The study is published in Nucleic Acids Research<\/a>.<\/p>\n

\"\"<\/a>Dr. Chathura J. Gunasekara<\/strong><\/p>\n

The study focused on a definitive characteristic of metastable epialleles: systemic interindividual variation in DNA methylation \u2013 that is, methylation that is consistent across different tissues of an individual but varies among individuals. \u201cWe performed a comprehensive, unbiased scan of epigenetic variation across the entire mouse genome, analyzing DNA methylation patterns in three different tissues \u2013 liver, kidney and brain \u2013 from each of ten genetically identical mice,\u201d said co-first author Dr. Chathura J. Gunasekara<\/a>, a bioinformatics expert in the Waterland lab.<\/a><\/p>\n

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Out of millions of potential sites, we found only 29 metastable epialleles.\u201d<\/p>\n<\/blockquote>\n

\u201cAnother surprising finding was that maternal diet \u2013 specifically, supplementation with pro-methylation nutrients like folate and vitamin B12 \u2013 had no effect on the methylation of the newly-discovered metastable epialleles,\u201d said co-first author Uditha Maduranga, who contributed to the project as a bioinformatics analyst in the Waterland lab.<\/p>\n

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This differs from classic studies of mouse metastable epialleles such as Avy, which showed that maternal methyl donor supplementation increases their methylation.\u201d<\/p>\n<\/blockquote>\n

\u201cThe discovery of the dietary supplementation effect in Avy mice 20 years ago motivated us to search for metastable epialleles in humans,\u201d said Waterland. Those efforts led to the discovery of thousands of human genomic regions called CoRSIVs<\/a>, for correlated regions of systemic interindividual epigenetic variation. Most of these are influenced by genetic variation, so they are not metastable epialleles.<\/p>\n

\u201cIronically,\u201d continued Waterland, \u201cestablishment of DNA methylation at human CoRSIVs is very sensitive to the environment of the early embryo, just like at the Avy metastable epiallele. In addition, CoRSIVs are strongly implicated in human disease.\u201d The 10,000 human CoRSIVs \u2013 \u00a0versus only 29 metastable epialleles in inbred mice \u2013 indicate that most systemic interindividual epigenetic variation is associated with genetic variation.<\/p>\n

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Rather than the inbred mice used in biomedical research for decades,\u201d Waterland continues, \u201cour results indicate that outbred mice are likely a better model to understand how nutrition during development affects interindividual epigenetic variation in humans.\u201d<\/p>\n<\/blockquote>\n

Taylor Zhang, Jonathan N. Wells, Maria S. Baker, Eleonora Laritsky, Yumei Li, Cristian Coarfa and Yi Zhu also contributed to this work. The authors are affiliated with Baylor College of Medicine, Cornell University or University of California \u2013 Irvine.<\/p>\n

Funding for this project was provided by NIH\/NIDDK (1R01DK125562), USDA\/ARS (CRIS 3092-5-001-059), NIH R35-GM122550, NIH R01-DK136619, R01-DK136532 and USDA\/ARS (CRIS 58-3092-5-008).<\/p>\n

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