Dad's diet controls offspring phenotype

Using a fly model of paternally induced obesity, Öst et al. show that acute changes in paternal diet — as short as 24 hours — reprogram offspring metabolism without affecting growth and development. Paternal intergenerational metabolic reprogramming altered chromatin states and gene expression in the F₁ generation via mechanisms that are dependent on Polycomb proteins and the core heterochromatin machinery. Specifically, obesity susceptibility resulted from reduced stage-specific epigenetic regulation of histone H3 lysine 27 trimethylation (H3K27me3)- and H3K9me3-defined domains both in mature sperm and in offspring embryos. The authors propose a model whereby phenotype is evolutionarily encoded directly into the chromatin state of specific loci and suggest that this mechanism directionally controls phenotypic variation within a population. Analysing two murine and three human microarray data sets of adipose tissue samples from lean and obese individuals, the team identified conserved gene signatures for epigenetically defined phenotypic variation.