Fig. 7: Schematic model that summarises the widespread reorganisation of gene regulatory interactions between naive and primed PSCs.

A substantial rewiring of promoter interactions occurs between naive and primed PSCs. Very few active enhancers are shared between naive (left) and primed (right) PSCs, and this divergence corresponds to important differences in the activity of key cell identity genes. Active enhancers in naive PSCs (light blue) are decommissioned predominantly through the gain of DNA methylation (black circles) during the transition into a primed state, and a minority acquire H3K27me3 (red circles) instead. The differences in enhancer activity are associated with the widespread reorganisation of OCT4, SOX2 and NANOG pluripotency factor binding, suggesting the presence of distinct, transcription factor-defined gene regulatory networks between PSC states. Many promoters were linked by long-range H3K27me3-associated interactions that formed de novo during the transition from the naive to the primed state, creating a strong spatial network of over 600 developmental genes.