Epigenetic processes control the parental-specific (imprinted) expression of a subset of mammalian genes. For example, the paternally expressed imprinted long non-coding (lnc) RNA Airn initiates paternal-specific silencing of Igf2r, a gene that is essential for development. Airn initiation of Igf2r silencing is followed by gain of DNA methylation on the silent Igf2r promoter. Here (), Denise Barlow, Florian Pauler and colleagues investigate the control of Igf2r silencing during mouse embryonic stem cell (ESC) differentiation. By turning Airn expression off during ESC differentiation, the researchers show that continuous Airn expression is needed to maintain Igf2r silencing until the paternal Igf2r promoter is methylated. By conditionally turning Airn expression on, they show that Airn can initiate Igf2r silencing throughout ESC differentiation and that silencing is maintained in the absence of DNA methylation. Thus, Airn lncRNA is necessary and sufficient to silence Igf2r throughout ESC development whereas DNA methylation is dispensable for silencing initiation and maintenance but reinforces Igf2r silencing.
