title: Genetic and Epigenetic Variation, but Not Diet, Shape the Sperm Methylome.
abstract: Paternal diet can impact metabolic phenotypes in offspring, but mechanisms underlying such intergenerational information transfer remain obscure. Here, we interrogate cytosine methylation patterns in sperm obtained from mice consuming one of three diets, generating whole genome methylation maps for four pools of sperm samples and for 12 individual sperm samples, as well as 61 genome-scale methylation maps. We find that "epivariation," either stochastic or due to unknown demographic or environmental factors, was a far stronger contributor to the sperm methylome than was the diet consumed. Variation in cytosine methylation was particularly dramatic over tandem repeat families, including ribosomal DNA (rDNA) repeats, but rDNA methylation was strongly correlated with genetic variation in rDNA copy number and was not influenced by paternal diet. These results identify loci of genetic and epigenetic lability in the mammalian genome but argue against a direct role for sperm cytosine methylation in dietary reprogramming of offspring metabolism.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Shea
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Serra
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.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Bioinformatics Core, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Hennady P
authors.initials: HP
authors.lastname: Shulha
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Bioinformatics Core, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Alper
authors.initials: A
authors.lastname: Kucukural
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ziller
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Markus P
authors.initials: MP
authors.lastname: Vallaster
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Hongcang
authors.initials: H
authors.lastname: Gu
authors.affiliation: Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01604, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Tapper
authors.affiliation: Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01604, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Gardner
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Meissner
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Bioinformatics Core, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Garber
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: oliver.rando@umassmed.edu.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rando
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics*; D004032:Diet; D044127:Epigenesis, Genetic / Q000235:genetics*; D057890:Epigenomics; D014644:Genetic Variation; D016678:Genome / Q000235:genetics*; D008297:Male; D051379:Mice; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D004275:DNA, Ribosomal