Genetic and Epigenetic Variation, but Not Diet, Shape the Sperm Methylome
Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology; Bioinformatics Core; Department of Psychiatry, Brudnick Neuropsychiatric Research Institute
Biochemistry | Bioinformatics | Cell Biology | Computational Biology | Developmental Biology | Genetics | Genomics | Molecular Biology | Translational Medical Research
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.
DOI of Published Version
Dev Cell. 2015 Dec 21;35(6):750-8. doi: 10.1016/j.devcel.2015.11.024. Link to article on publisher's site
Shea, Jeremy; Serra, Ryan W.; Carone, Benjamin R.; Shulha, Hennady P.; Kucukural, Alper; Ziller, Michael; Vallaster, Markus; Gu, Hongcang; Tapper, Andrew R.; Gardner, Paul D.; Meissner, Alexander; Garber, Manuel; and Rando, Oliver J., "Genetic and Epigenetic Variation, but Not Diet, Shape the Sperm Methylome" (2015). UMass Center for Clinical and Translational Science Supported Publications. 64.