We have a long-standing interest in the mammalian Cbx family members (Cbx2, 4, 6, 7 and 8), which are homologs of the single Drosophila Polycomb (Pc) protein. Previously, we examined the histone methylation binding preferences of the Cbx family members as well as their association with facultative heterochromatin, such as the inactive X chromosome. We and others have reported Cbx7 to be the predominant Pc protein expressed in mouse embryonic stem cells (ESCs), where it acts to maintain self-renewal and pluripotency. Upon ESC differentiation the expression of Cbx7 is downregulated, preceding the upregulation of other family members including, Cbx2, Cbx4, and Cbx8. Recently, we reported a novel phosphorylation site on mouse Cbx7 at residue Thr-118 (Cbx7T118ph), which is mediated by the MAPK signaling. This suggests that extracellular signaling can communicate directly and rapidly to chromatin. We are continuing our studies of Polycomb proteins in the context of cancer, with a focus on their role in tumor initiating cell biology.