Figure 7. Model of TF binding to enhancer classes during commitment from naïve pluripotency.

Diagram summarizing the changes occurring at decommissioned or maintained enhancers during commitment from naïve pluripotency. Decreased NANOG levels, although reversible, facilitate subsequent decrease in the levels of other naïve pluripotency TFs, including Esrrb and Klf4. Downregulation of these TFs triggers irreversible changes in the pool of active enhancers and marks commitment to differentiation. Class I enhancers are regions where OCT4 occupancy depends on the robust binding of naïve TF. These elements are decommissioned during commitment, losing histone acetylation and accumulating DNA methylation. Other enhancers, on average showing less pronounced binding of naïve TFs, retain OCT4 and active histone marks in primed pluripotent cells. These elements constitute a core of “primed” regulatory elements bound by OCT4 that may serve to nucleate the regulatory architecture through which lineage‐specific TFs collaborate with Oct4 to specify the early post‐implantation epiblast identity.