Top panel depicts the Dppa2/4 locus on mouse chromosome 16 or human chromosome 3. Dppa2/4 promoters are unmethylated in the germ line (top row) and preimplantation embryos (second row) where Dppa2/4 are expressed, and kept silent by promoter DNA methylation from E7.5 onwards (third row) and throughout the remainder of embryogenesis and in adult cells (bottom row). Bottom panel depicts the structure of Dppa2 and Dppa4 proteins showing SAP domain that binds DNA (green) and C-terminal domain (red) that binds histones. Residues sumoylated in ESCs are shown in circles. Numbers correspond to mouse Dppa2/4. Full length Dppa4 is found in most cell types while an alternatively spliced isoform found lacking the SAP domain is found in 2-cell embryos.