title: Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.
abstract: 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 Ppara. 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.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Carone
authors.forename: Lucas
authors.initials: L
authors.lastname: Fauquier
authors.forename: Naomi
authors.initials: N
authors.lastname: Habib
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Shea
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Hart
authors.forename: Ruowang
authors.initials: R
authors.lastname: Li
authors.forename: Christoph
authors.initials: C
authors.lastname: Bock
authors.forename: Chengjian
authors.initials: C
authors.lastname: Li
authors.forename: Hongcang
authors.initials: H
authors.lastname: Gu
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Zamore
authors.forename: Alexander
authors.initials: A
authors.lastname: Meissner
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
authors.forename: Hans A
authors.initials: HA
authors.lastname: Hofmann
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rando
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways; D002784:Cholesterol / Q000096:biosynthesis; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation; D018753:Diet, Protein-Restricted; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice
chemical_list: D003596:Cytosine; D002784:Cholesterol