Understanding regulation of Polycomb Repressor Complex 1 in embryonic stem cell self renewal and cellular proliferation

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

Polycomb-group (PcG) repressor proteins are key epigenetic regulators involved in both establishing gene expression patterns and maintaining long-term cellular memory. Maintenance of cellular gene expression memory is an important process in regulation of embryonic stem cell self renewal, cell identity, cell proliferation and tumor development (Sparmann and van Lohuzin 2006).
PcG proteins form large multi-protein complexes. The Polycomb Repressor Complex 1 (bmiPRC1) containing the Bmi1 subunit has been shown to be an E3 ubiquitin ligase that modifies chromatin by mono-ubiquitylation of histone H2A lysine 119. This epigenetic modification has been associated with gene repression (Wang et al. 2004). In mammalian cells multiple paralogues for the core PRC1 subunits have been identified. Recently we have identified a novel PRC1-like complex melPRC1 which contains the Bmi1 paralogue Mel-18. Additionally we have found that melPRC1 mediates gene repression through mono-ubiquitylation of H2A lysine 119 is regulated by phosphorylation (Elderkin et al. 2007).

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