The maintenance of embryonic stem (ES) cell pluripotency depends on a core transcriptional regulatory network that represses key transcription factors involved in differentiation and development. The Polycomb group (PcG) of proteins mediate the heritable silencing of developmental regulators, but are the PcG proteins and this transcriptional network functionally linked? Endoh and co-workers now show that the Polycomb repressive complex 1 (PRC1)components Ring1A/B act downstream of the core transcriptional regulatory circuitry that maintains mouse ES cell self renewal (see ). Ring1A/B,they show, are essential for maintaining undifferentiated ES cells through their repression of certain developmental regulators that direct ES cell differentiation. This silencing, which is achieved through the inhibition of chromatin remodelling, depends on a key component of the core transcription network: Oct3/4. But Oct3/4 also binds to these targets independently of PRC1. These and other results clearly show that a functional link between Ring1A/B-mediated PRC1 silencing and the core transcriptional regulatory circuitry acts to maintain ES cell self renewal.
