Publication Date:
2014-07-12
Description:
Adverse prenatal environments can promote metabolic disease in offspring and subsequent generations. Animal models and epidemiological data implicate epigenetic inheritance, but the mechanisms remain unknown. In an intergenerational developmental programming model affecting F2 mouse metabolism, we demonstrate that the in utero nutritional environment of F1 embryos alters the germline DNA methylome of F1 adult males in a locus-specific manner. Differentially methylated regions are hypomethylated and enriched in nucleosome-retaining regions. A substantial fraction is resistant to early embryo methylation reprogramming, which may have an impact on F2 development. Differential methylation is not maintained in F2 tissues, yet locus-specific expression is perturbed. Thus, in utero nutritional exposures during critical windows of germ cell development can impact the male germline methylome, associated with metabolic disease in offspring.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404520/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404520/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Radford, Elizabeth J -- Ito, Mitsuteru -- Shi, Hui -- Corish, Jennifer A -- Yamazawa, Kazuki -- Isganaitis, Elvira -- Seisenberger, Stefanie -- Hore, Timothy A -- Reik, Wolf -- Erkek, Serap -- Peters, Antoine H F M -- Patti, Mary-Elizabeth -- Ferguson-Smith, Anne C -- 095606/Wellcome Trust/United Kingdom -- 095645/Wellcome Trust/United Kingdom -- P30 DK036836/DK/NIDDK NIH HHS/ -- P30DK036836/DK/NIDDK NIH HHS/ -- R00 HD064793/HD/NICHD NIH HHS/ -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):1255903. doi: 10.1126/science.1255903. Epub 2014 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. ; Research Division, Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA. ; The Babraham Institute, Babraham, Cambridge, and Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. ; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. Faculty of Sciences, University of Basel, Basel, Switzerland. Swiss Institute of Bioinformatics, Basel, Switzerland. ; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. Faculty of Sciences, University of Basel, Basel, Switzerland. ; Research Division, Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA. afsmith@mole.bio.cam.ac.uk mary.elizabeth.patti@joslin.harvard.edu. ; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. afsmith@mole.bio.cam.ac.uk mary.elizabeth.patti@joslin.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25011554" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Caloric Restriction
;
*DNA Methylation
;
Epigenesis, Genetic
;
Female
;
Fetal Nutrition Disorders/genetics/*metabolism
;
Insulin/secretion
;
Male
;
Metabolic Diseases/metabolism
;
Mice
;
Mice, Inbred ICR
;
Nucleosomes/metabolism
;
Pregnancy
;
*Prenatal Exposure Delayed Effects
;
Spermatozoa/*metabolism/physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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