Imprinted DNA methylation reprogramming during early mouse embryogenesis at the Gpr1-Zdbf2 locus is linked to long cis-intergenic transcription

The paternally-expressed imprinted genes Gpr1 and Zdbf2 form a gene cluster wherein the imprinted-methylated regions of these two genes differ. We identified a novel, paternally expressed, long intergenic non-coding Zdbf2 variant (Zdbf2linc) transcribed from maternally methylated Gpr1 DMR during early embryogenesis in the mouse. While the Gpr1 DMR displayed biallelic hypermethylation, Zdbf2linc expression was rarely observed in the post-gastrulation, despite a positive correlation between the methylation of Zdbf2 DMRs and the mono-allelic transcription of the original Zdbf2 coding variant. Furthermore, lack of the maternal methylation imprint resulted in the biallelic expression of both coding and non-coding Zdbf2 transcripts as well as complete methylation of Zdbf2 DMRs. Globally, our findings suggest the role of Zdbf2linc in the establishment of secondary epigenetic modifications after implantation.

► Imprinted Zdbf2 gene expression is controlled by maternal methylation.
► A novel, long imprinted Zdbf2 variant is identified in mouse early embryos.
► The long variant is transcribed from the maternally methylated Gpr1 DMR.
► The Gpr1 DMR is biallelically methylated after gastrulation.
► Paternally methylated Zdbf2 DMRs are secondary DMRs.