Paternally-induced transgenerational environmental reprogramming of metabolic gene expression in mammals

By Benjamin R. Carone, Lucas Fauquier, Naomi Habib, Jeremy M. Shea, C. Hart, Ruowang Li, Christoph Bock, Chengjiang Li, Phillip D. Zamore, Alexander Meissner and 4 more. Cell, 2010

1,118 citations recorded by the source corpus.

SUMMARY Epigenetic information can be inherited through the mammalian germline, and represents a plausible transgenerational carrier of environmental information. To test whether transgenerational inheritance of environmental information occurs in mammals, we carried out an expression profiling screen for genes in mice that responded to paternal diet. Offspring of males fed a low protein diet exhibited elevated hepatic expression of many genes involved in lipid and cholesterol biosynthesis, and decreased levels of cholesterol esters, relative to the offspring of males fed a control diet. Epigenomic profiling of offspring livers revealed numerous modest (~20%) changes in cytosine methylation depending on paternal diet, including reproducible changes in methylation over a likely enhancer for the key lipid regulator PPARα. These results, in conjunction with recent human epidemiological data, indicate that parental diet can affect cholesterol and lipid metabolism in offspring, and define a model system to study environmental reprogramming of the heritable epigenome.

Subfields: Molecular Biology, Pediatrics, Perinatology and Child Health, Physiology

View Paper: https://www.semanticscholar.org/paper/38db5055cccbdf5d92c4938b20151235f3c3e769

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In Molecular Biology

1. Wolf Reik
2. W. Dean
3. Jörn Walter
4. Felix Krueger
5. Fátima Santos
6. Simon R. Andrews
7. Stephan Beck
8. M. Fraga

In Pediatrics, Perinatology and Child Health

1. Wolf Reik
2. Jörn Walter
3. W. Dean
4. Fátima Santos
5. Stephan Beck
6. Linda Partridge
7. Luigi Fontana
8. T. Bale

In Physiology

1. Luigi Fontana
2. Linda Partridge
3. G. Koob

Citations in the corpus

• Epigenetics and the environment: emerging patterns and implications (2012, background): “These alterations were associated with minor DNA methylation changes, including reduced levels of methylation at a putative enhancer of Ppara”
• The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells (2012, background): “These CGIs may be candidates for short-term transgenerational inheritance in mammals, which seems variable in its persistence and hence heritability (Jimenez-Chillaron et al., 2009; Carone et al., 2010; Ng et al., 2010; Daxinger and Whitelaw, 2012).”
• Promoting Health and Longevity through Diet: from Model Organisms to Humans (2015, positive): “%) changes in DNA cytosine methylation in specific gene regions, including a putative enhancer for the lipid regulator Ppara (Carone et al., 2010).”
• Epigenome-Wide Association Studies for common human diseases (2011, background): “It has recently been demonstrated that feeding F 0 generation male mice either a high-fat or low-protein diet from weaning to the time of mating results in F 1 offspring with altered metabolic phenotype”
• Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation (2013, background): “Furthermore, identification of offspring physiological and behavioral changes following direct paternal perturbations has highlighted sperm epigenetic marks as a potential mechanism of transmission (Carone et al., 2010; Ng et al., 2010; Dietz et al., 2011; Vassoler et al., 2013).”
• Transgenerational Epigenetic Inheritance: myths and mechanisms (2014, neutral): “Mice fed a low-protein diet passed on a high-cholesterol phenotype, with gene expression differences and modest DNA methylation differences to their paternal offspring (Carone et al., 2010; Radford et al., 2012).”
• Understanding transgenerational epigenetic inheritance via the gametes in mammals (2012, background): “Another study looking at the effects of paternal exposure to a low-protein diet in mice found that both male and female offspring showed detectable changes in expression of some lipid and cholesterol genes in the live”
• Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals (2015, background): “…culture to obscure paternal effects on offspring metabolism, we nonetheless found that IVF-derived offspring of Low Protein males exhibited significant hepatic upregulation of the gene encoding the cholesterol biosynthesis enzyme squalene epoxidase, compared to Control IVF offspring (2)( Fig.”
• Regulation of animal size by eNPP, Bergmann's rule, and related phenomena (2011, background): “…health, and reproductive potential of children and even grandchildren (Pembrey et al. 2006, Heijmans et al. 2008, Whitelaw and Whitelaw 2008, Carone et al. 2010), emphasizes how quickly food quality and quantity, as well as other environmental conditions, can alter the body size and…”
• DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos (2014, background): “2011), and hypomethylation is correlated with active gene expression (Carone et al. 2010; Sandovici et al. 2011).”