Figure 2.

An epigenetic switch controls Dlk1 imprinting. (A) Throughout embryonic development Dlk1 is monoallelically expressed from the paternal allele in multiple neuronal tissues comprising the subventricular zone (SVZ) and striatum (St) among others and in non-neuronal tissues. Maternal silencing correlates with the absence of germline-derived DNA methylation at the intergenic differentially methylated regions (DMR) (yellow hexagon) which resides between the Dlk1 and Gtl2 genes and the absence of somatic methylation of the DMRs at the same genes (unfilled lollipops). Conversely, paternal expression associates with germline-derived methylation at the intergenic DMR (black hexagon) in concert with somatic methylation at the downstream DMRs at Dlk1 and Gtl2 (filled lollipops). Methylation patterns are identical in the SVZ (left scheme) and St (right scheme) at embryonic age. (B) Dlk1 is biallelically expressed in the SVZ but not in the St from postnatal day 7 onward and in adulthood. The paternal methylation pattern (i.e., methylation at the downstream Dlk1 DMR, the intergenic DMR but not the Gtl2 DMR) is largely adopted by the expressed maternal allele. At opposite, monoallelic Dlk1 expression together with the underlying methylation pattern are maintained in the St.