The role of Polycomb in stem cell genome architecture

Polycomb-group proteins maintain embryonic stem cell identity by repressing genes that encode for developmental regulatory factors. Failure to properly control developmental transcription programs by Polycomb proteins is linked to disease and embryonic lethality. Recent technological advances have revealed that developmentally repressed genes tend to cluster in the three-dimensional space of the nucleus. Importantly, spatial clustering of developmental genes is fundamental for the correct regulation of gene expression during early development. Here, we outline novel insights and perspectives regarding the function of Polycomb complexes in shaping the stem cell genome architecture, and discuss how this function might be required to properly orchestrate transcriptional programs during differentiation.