Role of Polycomb-group genes in sustaining activities of normal and malignant stem cells

Abstract

Polycomb-group genes (PcG), identified by Drosophila genetics, are believed to maintain positional information by constituting a cellular memory system. Recently this system has been proved to be supported by epigenetic transcription regulation. PcG products comprise two distinct complexes, PcG complex 1 and 2. First PcG complex 2 silences chromatin and encodes a histone code by methylating histone H3 at lysine 27. PcG complex 1 is, then, recruited by recognizing the histone code, and ubiquitinates histone H2A and/or inhibits chromatin remodeling to maintain the silenced states of the locus. Biologically, PcG-deficient mice provided biological evidence that PcG are essential for sustaining stem cell activity. More recently PcG were reported to be correlated with cancer progression and prognosis as well as with cancer stem cell activity. PcG may thus play a crucial part in sustaining the activities of malignant as well as normal stem cells. Although PcG were initially seen to maintain stem cell activity through repression of the INK4a locus, they now appear to perform more diverse functions in supporting stem cells. This paper summarizes current information on the molecular roles of PcG in normal and malignant stem cells and discusses the implications in future cancer therapy and regenerative medicine.