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Cell. 2014 Dec 4;159(6):1352-64. doi: 10.1016/j.cell.2014.11.005.

Paternal diet defines offspring chromatin state and intergenerational obesity.

Author information

1
Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany; Department of Clinical and Experimental Medicine, Linkoping University, 58183 Linkoping, Sweden. Electronic address: anita.ost@liu.se.
2
Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
3
Institut de Medicina Predictiva i Personalitzada del Càncer, Can Ruti Campus, Ctra. de Can Ruti, Camí de les Escoles s/n, 08916 Badalona, Barcelona, Spain; Josep Carreras Leukaemia Research Institute (IJC), ICO-Hospital GermansTrias i Pujol, 08916 Badalona, Barcelona, Spain.
4
Institut de Medicina Predictiva i Personalitzada del Càncer, Can Ruti Campus, Ctra. de Can Ruti, Camí de les Escoles s/n, 08916 Badalona, Barcelona, Spain.
5
Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, 1400-038 Lisbon, Portugal.
6
Systems Biology of Gene Regulatory Elements, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
7
Institute of Biology, Developmental Genetics, Martin Luther University Halle, 06120 Halle, Germany.
8
Department of Clinical and Experimental Medicine, Linkoping University, 58183 Linkoping, Sweden.
9
Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany. Electronic address: pospisilik@ie-freiburg.mpg.de.

Abstract

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.

PMID:
25480298
DOI:
10.1016/j.cell.2014.11.005
[Indexed for MEDLINE]
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