Embryonic stem cells (ESCs) are immortal cell lines derived from the peri-implantation mammalian embryo. Both ESCs and the embryos from which they are derived are remarkable, in that individual cells retrain the capacity to begin developmental anew, despite having undergone a degree of patterning or differentiation. What is the basis for this plasticity at a transcriptional level? We have identified two new mechanisms regulating this process. The first involves a protective activity of Polycomb co-repressor complexes, that enables transcriptional stimulation in the absence of commitment. The second relies on the reversible disengagement of RNA Polymerase II from specific promoters in response to signaling. I will discuss these mechanisms and how they impact on the capacity of ESCs to retain their plasticity while they prime for differentiation but continue in self-renewal. .