학술논문
Paternal Diet Defines Offspring Chromatin State and Intergenerational Obesity.
Document Type
Article
Author
Öst, Anita; Lempradl, Adelheid; Casas, Eduard; Weigert, Melanie; Tiko, Theodor; Deniz, Merdin; Pantano, Lorena; Boenisch, Ulrike; Itskov, Pavel M.; Stoeckius, Marlon; Ruf, Marius; Rajewsky, Nikolaus; Reuter, Gunter; Iovino, Nicola; Ribeiro, Carlos; Alenius, Mattias; Heyne, Steffen; Vavouri, Tanya; Pospisilik, J. Andrew
Source
Subject
*CHROMATIN
*ANIMAL models in research
*OBESITY
*EPIGENETICS
*DROSOPHILA genetics
*EXONS (Genetics)
*GERM cells
*DISEASE susceptibility
*BIOLOGICAL variation
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Language
ISSN
0092-8674
Abstract
Summary 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 i nter g enerational m etabolic r eprogramming (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. [ABSTRACT FROM AUTHOR]