Expression patterns of long noncoding RNAs from Dlk1-Dio3 imprinted region and the potential mechanisms of Gtl2 activation during blastocyst development

The function of long noncoding RNAs (lncRNAs) in cell differentiation and development have begun to be revealed in recent years. However, the expression pattern and mechanisms regulating lncRNAs are largely unknown during mammalian preimplantation development. LncRNAs expressed from Dlk1-Dio3 imprinted region have been linked to pluripotency of induced pluripotent cells (iPSCs). In this study we show that these lncRNAs (Gtl2, Rian and Mirg) are first expressed at the morula stage and gradually restricted to the inner cell mass (ICM) as the embryo differentiates into the blastocyst. Analysis of DNA methylation at IG-DMR and Gtl2-DMR showed no change during preimplantation while the presence of the activating histone modification H3K4me3 increased significantly from 8-cell to blastocyst stage, which may explain the expression activation. Additionally, knockdown of transcription factors (Oct4, Sox2 and Nanog) in blastocyst reduced the expression of Gtl2, indicating pluripotency factors regulate transcription of these lncRNAs. This study provides the spatiotemporal expression and dynamic changes of lncRNAs from Dlk1-Dio3 imprinted region in mouse preimplantation stage embryos and offers insight into the potential mechanisms responsible for Gtl2 activation.