Sensitive Flow Cytometric Analysis Reveals a Novel Type of Parent-of-Origin Effect in the Mouse Genome

Abstract

The discovery of classic parental imprinting came, at least in part, from the analysis of transgene expression in mice [1]. It was noticed that some transgenes were only expressed following paternal transmission [2–4] and that others sometimes showed differential patterns of methylation depending on the parent of origin [5, 6]. Here, we present evidence of a novel and more subtle form of parental imprinting by taking advantage of the highly sensitive detection of murine transgene expression afforded by flow cytometry. We have produced nine lines of transgenic mice carrying a GFP reporter linked to the human α-globin promoter and enhancer elements, which direct expression to erythroid cells. A high proportion of transgenic lines, four of the nine, display significantly lower levels of expression following maternal transmission. Both the percentage of expressing cells and the mean fluorescence in expressing cells are between 10% and 30% lower following maternal transmission. These effects are reversible upon passage through the opposite germline. This finding raises the possibility that differences in the epigenetic state of the maternal and paternal chromosomes in adult somatic cells are more widespread than was previously thought.