Fig. 7

DNA methylation Controls the Balance of NANOG and SOX17 in hPGC Specification. A NANOG, SMAD2/3, TET1 ChIP-seq binding sites and methylation profile for the SOX17 and NANOG locus, red area indicated promoter region; B Density-scatterplot showing differentially methylated promoters in TKO day4 embryoids and WT day4 hPGCLCs; C GO analysis of hypermethylation and hypomethylation promoters in B; D ChIP-qPCR for TET1 in WT day4 embryoids in NANOG and SOX17 promoters; E ChIP-qPCR for NANOG in WT day4 embryoids in SOX17 promoters; F A hypothesis for epigenetic regulation of hPGC fate. The balance between NANOG and SOX17 mediated by TETs and DNMT3B guarantees hPGC specification from pluripotent cells. Overexpression of SOX17 or NANOG would compel cells to endoderm or meso/ectoderm germ layers, respectively; G A model illustrating the different functions of NANOG for PGC specification in mice (top) and humans (bottom). In mice, NANOG activates the expression of Blimp1 and Prdm14 by binding to their enhancers, which could be repressed by Sox2 during mPGC induction in vitro. In humans, TET1 and DNMT3B work oppositely to regulate NANOG expression during hPGC induction in vitro. And NANOG further regulates SOX17 expression by binding to its promoter