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Paternal Diet Defines Offspring Chromatin State and Intergenerational Obesity

Öst, Anita (author)
Linköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet,Max Planck Institute Immunobiol and Epigenet, Germany
Lempradl, Adelheid (author)
Max Planck Institute Immunobiol and Epigenet, Germany
Casas, Eduard (author)
Institute Medical Predict and Personalitzada Canc, Spain; ICO Hospital GermansTrias and Pujol, Spain
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Weigert, Melanie (author)
Max Planck Institute Immunobiol and Epigenet, Germany
Tiko, Theodor (author)
Max Planck Institute Immunobiol and Epigenet, Germany
Deniz, Merdin (author)
Max Planck Institute Immunobiol and Epigenet, Germany
Pantano, Lorena (author)
Institute Medical Predict and Personalitzada Canc, Spain
Boenisch, Ulrike (author)
Max Planck Institute Immunobiol and Epigenet, Germany
Itskov, Pavel M. (author)
Champalimaud Centre Unknown, Portugal
Stoeckius, Marlon (author)
Max Delbruck Centre Molecular Med, Germany
Ruf, Marius (author)
Max Planck Institute Immunobiol and Epigenet, Germany
Rajewsky, Nikolaus (author)
Max Delbruck Centre Molecular Med, Germany
Reuter, Gunter (author)
University of Halle Wittenberg, Germany
Iovino, Nicola (author)
Max Planck Institute Immunobiol and Epigenet, Germany
Ribeiro, Carlos (author)
Champalimaud Centre Unknown, Portugal
Alenius, Mattias (author)
Linköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet
Heyne, Steffen (author)
Max Planck Institute Immunobiol and Epigenet, Germany
Vavouri, Tanya (author)
Institute Medical Predict and Personalitzada Canc, Spain; ICO Hospital GermansTrias and Pujol, Spain
Pospisilik, J. Andrew (author)
Max Planck Institute Immunobiol and Epigenet, Germany
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 (creator_code:org_t)
Elsevier (Cell Press), 2014
2014
English.
In: Cell. - : Elsevier (Cell Press). - 0092-8674 .- 1097-4172. ; 159:6, s. 1352-1364
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  • Journal article (peer-reviewed)
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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