Superseries_Endoh2008_PcG_Pou5f1

The Polycomb group (PcG) gene products mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes-1 (PRC1) and -2 (PRC2). PRC2 catalyses trimethylation of histone H3 at lysine 27 (H3K27) which in turn is thought to provide a recruitment site for PRC1. Recent studies demonstrate that mono-ubiquitylation of histone H2A at lysine 119 is important in PcG mediated silencing with the core PRC1 component Ring1A/B functioning as the E3 ligase8. PRC2 has been shown to share target genes with the core transcription network to maintain embryonic stem (ES) cells including Oct4 and Nanog. Here we identify an essential role for PRC1 in repressing developmental regulators in ES cells, and thereby in maintaining ES cell pluripotency. A significant proportion of the PRC1 target genes are also repressed by Oct4. We demonstrate that engagement of PRC1 and PRC2 at target genes is Oct4-dependent and moreover that Ring1B interacts with Oct4. Collectively these results show that PcG complexes are instrumental in Oct4-dependent repression required to maintain pluripotency of ES cells. This study provides a first functional link between a core ES cell regulator and global epigenetic regulation of the genome. This SuperSeries is composed of the SubSeries listed below. This study is designed to investigate a functional link between a core ES cell regulator and global epigenetic regulation. ChIP-chip experiments (GSM266076 and GSM266077) revealed the Ring1B-binding sites in promoter regions in ES cells. Microarray experiments were also performed (GSM265040 and GSM265041 for Ring1B KO, GSM265042 and GSM265043 for Ring1A and Ring1B double KO, and GSM265044, GSM265045 and GSM266115 for Oct3/4 KO). Our study focused how these genes interplay in the regulation of gene expression in ES cells.