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Paternal Diet Defines Offspring Chromatin State and Intergenerational Obesity
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Max Planck Institute Immunobiol and Epigenet, Germany.
Max Planck Institute Immunobiol and Epigenet, Germany.
Institute Medical Predict and Personalitzada Canc, Spain; ICO Hospital GermansTrias and Pujol, Spain.
Max Planck Institute Immunobiol and Epigenet, Germany.
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2014 (English)In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 159, no 6, 1352-1364 p.Article in journal (Refereed) Published
Abstract [en]

The global rise in obesity has revitalized a search for genetic and epigenetic factors underlying the disease. We present a Drosophila model of paternal-diet-induced intergenerational metabolic reprogramming (IGMR) and identify genes required for its encoding in offspring. Intriguingly, we find that as little as 2 days of dietary intervention in fathers elicits obesity in offspring. Paternal sugar acts as a physiological suppressor of variegation, desilencing chromatin-state-defined domains in both mature sperm and in offspring embryos. We identify requirements for H3K9/K27me3-dependent reprogramming of metabolic genes in two distinct germline and zygotic windows. Critically, we find evidence that a similar system may regulate obesity susceptibility and phenotype variation in mice and humans. The findings provide insight into the mechanisms underlying intergenerational metabolic reprogramming and carry profound implications for our understanding of phenotypic variation and evolution.

Place, publisher, year, edition, pages
Elsevier (Cell Press) , 2014. Vol. 159, no 6, 1352-1364 p.
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-113500DOI: 10.1016/j.cell.2014.11.005ISI: 000346652900014PubMedID: 25480298OAI: diva2:781933

Funding Agencies|Max-Planck Society; EU (NoE Epigenesys); ERC [281641]; Swedish VR [K2011-78PK-21893-01-2]; SSMF grants; Spanish Ministry grant [BFU2011-30246, RYC-2010-07114]; Marie Curie European Reintegration Grant "Evo-Chromo; IMPPC; Champalimaud Foundation; Human Frontiers Program Project Grant [RGP0022/2012]; Portuguese Foundation for Science and Technology (FCT) grant [PTDC/BIA-BCM/118684/2010]; Foundation for Science and Technology [SFRH/BPD/79325/2011]

Available from: 2015-01-19 Created: 2015-01-19 Last updated: 2015-01-19

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Öst, AnitaAlenius, Mattias
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