Intergenerational epigenetic inheritance

Some prenatal exposures are known to affect offspring and subsequent generations through non-mendelian epigenetic inheritance. Now, Mary-Elizabeth Patti, Anne Ferguson-Smith and colleagues shed light on the epigenetic mechanisms of intergenerational inheritance following in utero undernourishment in mice (Science doi:10.1126/science.1255903, 10 July 2014). The authors imposed maternal nutritional restriction during the time when male primordial germ cells are epigenetically reprogrammed in developing embryos and assessed the whole-genome distribution of methylation in the sperm of F₁ animals using immunoprecipitation of methylated DNA followed by high-throughput sequencing. They identified 166 differentially methylated regions (DMRs), most of which were hypomethylated and were preferentially located in intergenic regions and CpG islands. The authors found that differential methylation was not present in liver and brain samples from F₂ generation animals, although they did observe changes in the expression of genes neighboring DMRs. This work shows that in utero exposure to an adverse environment can affect genome-wide patterns of methylation in the male germ line.