The controversial role of the Polycomb group proteins in transcription and cancer : how much do we not understand Polycomb proteins?

Polycomb group proteins (PcGs) are a large protein family that includes diverse biochemical features assembled together in two large multiprotein complexes. These complexes maintain gene transcriptional repression in a cell type specific manner by modifying the surrounding chromatin to control development, differentiation and cell proliferation. PcGs are also involved in several diseases. PcGs are often directly or indirectly implicated in cancer development for which they have been proposed as potential targets for cancer therapeutic strategies. However, in the last few years a series of discoveries about the basic properties of PcGs and the identification of specific genetic alterations affecting specific Polycomb proteins in different tumours have converged to challenge old dogmas about PcG biological and molecular functions. In this review, we analyse these new data in the context of the old knowledge, highlighting the controversies and providing new models of interpretation and ideas that will perhaps bring some order among apparently contradicting observations. Polycomb group proteins (PcGs) assemble two large complexes with different biochemical features ensuring gene transcriptional repression in a cell-type specific manner by modifying the surrounding chromatin. PcGs control development, differentiation, cell proliferation and are involved in cancer onset. This review analyzes new evidences challenging old dogmas about PcG functions, highlighting the controversies and providing new models to interpret PcG activities.